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Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of
granulocyte Granulocytes are cells in the innate immune system The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutiona ...
s and make up 40% to 70% of all
white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the cells of the immune system The immune system is a network of biological processes that protects an organism In biology, an organism (from Ancient Greek, Greek: ...
s in humans. They form an essential part of the
innate immune system The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the d ...

innate immune system
, with their functions varying in different animals. They are formed from
stem cell In multicellular organisms Multicellular organisms are organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any individual contiguous system that embodies the Life#Biology, properties ...
s in the
bone marrow Bone marrow is a semi-solid tissue Tissue may refer to: Biology * Tissue (biology), an ensemble of similar cells that together carry out a specific function * ''Triphosa haesitata'', a species of geometer moth found in North America * ''Triphos ...
and differentiated into subpopulations of neutrophil-killers and neutrophil-cagers. They are short-lived and highly motile, or mobile, as they can enter parts of tissue where other cells/molecules cannot. Neutrophils may be subdivided into segmented neutrophils and banded neutrophils (or
bands Band or BAND may refer to: Places *Bánd, a village in Hungary *Band, Iran, a village in Urmia County, West Azerbaijan Province, Iran *Band, Mureș, a commune in Romania *Band-e Majid Khan, a village in Bukan County, West Azerbaijan Province, Ira ...
). They form part of the polymorphonuclear cells family (PMNs) together with
basophil Basophils are a type of white blood cells, white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsib ...

basophil
s and
eosinophil Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the cells of the immune system The immune system is a network o ...

eosinophil
s. The name ''neutrophil'' derives from staining characteristics on
hematoxylin Haematoxylin or hematoxylin (), also called natural black 1 or C.I. 75290, is a compound Compound may refer to: Architecture and built environments * Compound (enclosure), a cluster of buildings having a shared purpose, usually inside a fen ...
and
eosin Eosin is the name of several fluorescent acidic compounds which bind to and form salts with basic, or eosinophilic, compounds like proteins containing amino acid residues such as arginine and lysine, and stains them dark red or pink as a resul ...

eosin
( H&E)
histological Histology, also known as microscopic anatomy or microanatomy, is the branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Mol ...

histological
or cytological preparations. Whereas
basophilic A Basophil granulocyte stains dark purple upon H&E staining. Basophilic is a technical term used by pathologists. It describes the microscopic appearance of cells and tissues, as seen down the microscope A microscope (from the grc, μι ...
white blood cells stain dark blue and
eosinophilic Eosinophilic (Greek suffix -phil- A philia is the love or Fixation (psychology), obsession with a particular thing or subject. The suffix -philia is used to specify the love or obsession with something more specific. It is antonymic to -phobia. ...
white blood cells stain bright red, neutrophils stain a neutral pink. Normally, neutrophils contain a nucleus divided into 2–5 lobes. Neutrophils are a type of
phagocyte Phagocytes are cell (biology), cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or Apoptosis, dying cells. Their name comes from the Greek language, Greek ', "to eat" or "devour", and "-cyte", the suffix in ...
and are normally found in the
blood Blood is a body fluid Body fluids, bodily fluids, or biofluids are liquid A liquid is a nearly incompressible In fluid mechanics or more generally continuum mechanics, incompressible flow (isochoric process, isochoric flow) refers t ...

blood
stream. During the beginning (
acute Acute may refer to: Science and technology * Acute angle ** Acute triangle ** Acute, a leaf shape in the glossary of leaf morphology#acute, glossary of leaf morphology * Acute (medicine), a disease that it is of short duration and of recent onset. ...
) phase of
inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogen In biology Biology is the natural science that studies life and living organisms, including their anato ...
, particularly as a result of
bacteria Bacteria (; common noun bacteria, singular bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typ ...

bacteria
l
infection An infection is the invasion of an organism's body tissues by disease-causing agents, their multiplication, and the reaction of host A host is a person responsible for guests at an event or for providing hospitality during it. Host may ...

infection
, environmental exposure, and some cancers, neutrophils are one of the first responders of inflammatory cells to migrate toward the site of inflammation. They migrate through the blood vessels and then through
interstitial An interstitial space or interstice is a space between structures or objects. In particular, interstitial may refer to: Biology * Interstitial cell tumor * Interstitial cell, any cell that lies between other cells * Interstitial collagenase, e ...
tissue, following chemical signals such as
interleukin-8 Interleukin 8 (IL-8 or chemokine (C-X-C motif) ligand 8, CXCL8) is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells and endothelial cells. Endothelial cells Endothelium is a single ...
(IL-8), C5a, fMLP,
Leukotriene B4 Leukotriene B4 (LTB4) is a leukotriene involved in inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a prote ...

Leukotriene B4
, and H2O2 in a process called
chemotaxis Chemotaxis (from '' chemo-'' + ''taxis A taxis (; ) is the movement Movement may refer to: Common uses * Movement (clockwork), the internal mechanism of a timepiece * Motion (physics), commonly referred to as movement Arts, entertainmen ...

chemotaxis
. They are the predominant cells in
pus Pus is an exudate An exudate is a fluid emitted by an organism through pores or a wound, a process known as exuding or exudation. ''Exudate'' is derived from ''exude'', "to ooze", from the Latin Latin (, or , ) is a classical language ...

pus
, accounting for its whitish/yellowish appearance. Neutrophils are recruited to the site of injury within minutes following trauma and are the hallmark of acute inflammation; however, due to some
pathogens In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanism ...
being indigestible, they might not be able to resolve certain infections without the assistance of other types of immune cells.


Structure

When adhered to a surface, neutrophil granulocytes have an average diameter of 12–15 
micrometers The micrometre ( international spelling as used by the International Bureau of Weights and Measures; SI symbol: μm) or micrometer ( American spelling), also commonly known as a micron, is an SI derived unit SI derived units are units of m ...
(µm) in peripheral blood smears. In suspension, human neutrophils have an average diameter of 8.85 µm. With the
eosinophil Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the cells of the immune system The immune system is a network o ...

eosinophil
and the
basophil Basophils are a type of white blood cells, white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsib ...
, they form the class of ''polymorphonuclear cells'', named for the
nucleus ''Nucleus'' (plural nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA ...

nucleus
' multilobulated shape (as compared to
lymphocyte A lymphocyte is a type of white blood cell in the immune system The immune system is a network of biological processes that protects an organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'' ...

lymphocyte
s and
monocyte Monocytes are a type of ''leukocyte'', or white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the cells of the immune system The immune system is a network of biological processes that protects an organi ...

monocyte
s, the other types of white cells). The nucleus has a characteristic lobed appearance, the separate lobes connected by
chromatin Chromatin is a complex of DNA Deoxyribonucleic acid (; DNA) is a molecule File:Pentacene on Ni(111) STM.jpg, A scanning tunneling microscopy image of pentacene molecules, which consist of linear chains of five carbon rings. A molecu ...
. The nucleolus disappears as the neutrophil matures, which is something that happens in only a few other types of nucleated cells. Up to 17% of female human neutrophil nuclei have a drumstick-shaped appendage which contains the inactivated X chromosome. In the cytoplasm, the
Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle In cell biology Cell biology (also cellular biology or cytology) is a branch of biology Biology is the natural science that stu ...

Golgi apparatus
is small,
mitochondria A mitochondrion (; ) is a double-membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Biological membranes include cell membranes ...

mitochondria
and
ribosome Ribosomes ( ), also called Palade granules, are molecular machine, macromolecular machines, found within all cell (biology), cells, that perform Translation (biology), biological protein synthesis (mRNA translation). Ribosomes link amino acids ...

ribosome
s are sparse, and the rough
endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...
is absent. The cytoplasm also contains about 200 granules, of which a third are azurophilic. Neutrophils will show increasing segmentation (many segments of the nucleus) as they mature. A normal neutrophil should have 3–5 segments. Hypersegmentation is not normal but occurs in some disorders, most notably vitamin B12 deficiency. This is noted in a manual review of the blood smear and is positive when most or all of the neutrophils have 5 or more segments. Neutrophils are the most abundant white blood cells in humans (approximately 1011 are produced daily); they account for approximately 50–70% of all white blood cells (leukocytes). The stated normal range for human blood counts varies between laboratories, but a neutrophil count of 2.5–7.5 × 109/L is a standard normal range. People of
Africa Africa is the world's second-largest and second-most populous continent A continent is any of several large landmass A landmass, or land mass, is a large region In geography Geography (from Greek: , ''geographia'', ...

Africa
n and
Middle East The Middle East ( ar, الشرق الأوسط, ISO 233 The international standard An international standard is a technical standard A technical standard is an established norm (social), norm or requirement for a repeatable technical task whi ...

Middle East
ern descent may have lower counts, which are still normal. A report may divide neutrophils into segmented neutrophils and
bands Band or BAND may refer to: Places *Bánd, a village in Hungary *Band, Iran, a village in Urmia County, West Azerbaijan Province, Iran *Band, Mureș, a commune in Romania *Band-e Majid Khan, a village in Bukan County, West Azerbaijan Province, Ira ...
. When circulating in the bloodstream and inactivated, neutrophils are spherical. Once activated, they change shape and become more amorphous or
amoeba An amoeba (; less commonly spelt ameba or amœba; plural ''am(o)ebas'' or ''am(o)ebae'' ), often called an amoeboid, is a type of cell or unicellular organism A unicellular organism, also known as a single-celled organism, is an organism ...

amoeba
-like and can extend pseudopods as they hunt for
antigen In immunology Immunology is a branch of biology that covers the study of immune systems in all organisms. Immunology charts, measures, and contextualizes the Physiology, physiological functioning of the immune system in states of both health ...
s. In 1973, Sanchez et al. found that the capacity of neutrophils to engulf bacteria is reduced when simple sugars like glucose, fructose as well as sucrose, honey and orange juice were ingested, while the ingestion of starches had no effect. Fasting, on the other hand, strengthened the neutrophils' phagocytic capacity to engulf bacteria. It was concluded that the function, and not the number, of phagocytes in engulfing bacteria was altered by the ingestion of sugars. In 2007 researchers at the Whitehead Institute of Biomedical Research found that given a selection of sugars on microbial surfaces, the neutrophils reacted to some types of sugars preferentially. The neutrophils preferentially engulfed and killed beta-1,6-glucan targets compared to beta-1,3-glucan targets.


Development


Life span

The average lifespan of inactivated human neutrophils in the circulation has been reported by different approaches to be between 5 and 135 hours. Upon activation, they marginate (position themselves adjacent to the blood vessel endothelium) and undergo
selectin The selectins (cluster of differentiation 62 or CD62) are a family of cell adhesion molecule File:Pentacene on Ni(111) STM.jpg, A scanning tunneling microscopy image of pentacene molecules, which consist of linear chains of five carbon rings. ...
-dependent capture followed by
integrin Integrins are transmembrane receptors Cell surface receptors (membrane receptors, transmembrane receptors) are receptor (biochemistry), receptors that are embedded in the cell membrane, plasma membrane of cell (biology), cells. They act in cell ...

integrin
-dependent adhesion in most cases, after which they migrate into tissues, where they survive for 1–2 days. Neutrophils are much more numerous than the longer-lived
monocyte Monocytes are a type of ''leukocyte'', or white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the cells of the immune system The immune system is a network of biological processes that protects an organi ...

monocyte
/
macrophage Macrophages (abbreviated as Mφ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the ...

macrophage
phagocytes. A
pathogen In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanism ...
(disease-causing microorganism or virus) is likely to first encounter a neutrophil. Some experts hypothesize that the short lifetime of neutrophils is an
evolution Evolution is change in the heritable Heredity, also called inheritance or biological inheritance, is the passing on of Phenotypic trait, traits from parents to their offspring; either through asexual reproduction or sexual reproduction, ...

evolution
ary adaptation. The short lifetime of neutrophils minimizes propagation of those pathogens that parasitize phagocytes because the more time such parasites spend outside a host cell, the more likely they will be destroyed by some component of the body's defenses. Also, because neutrophil
antimicrobial An antimicrobial is an agent that kills microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology, an organism () is any organic, life, living system that functions as an individual entity. All orga ...
products can also damage host
tissue Tissue may refer to: Biology * Tissue (biology), an ensemble of similar cells that together carry out a specific function * ''Triphosa haesitata'', a species of geometer moth found in North America * ''Triphosa dubitata'', a species of geometer mot ...
s, their short life limits damage to the host during
inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogen In biology Biology is the natural science that studies life and living organisms, including their anato ...
. Neutrophils will be removed after
phagocytosis Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis Endocytosis is a cellular process i ...

phagocytosis
of pathogens by macrophages. PECAM-1 and
phosphatidylserine Phosphatidylserine (abbreviated Ptd-L-Ser or PS) is a phospholipid and is a component of the cell membrane. It plays a key role in cell cycle signaling, specifically in relation to apoptosis. It is a key pathway for viruses to enter cells via apo ...

phosphatidylserine
on the cell surface are involved in this process.


Function


Chemotaxis

Neutrophils undergo a process called
chemotaxis Chemotaxis (from '' chemo-'' + ''taxis A taxis (; ) is the movement Movement may refer to: Common uses * Movement (clockwork), the internal mechanism of a timepiece * Motion (physics), commonly referred to as movement Arts, entertainmen ...

chemotaxis
via
amoeboid movementAmoeboid movement is the most common mode of locomotion in eukaryotic cells. It is a crawling-like type of movement accomplished by protrusion of cytoplasm In cell biology, the cytoplasm is all of the material within a Cell (biology), cell, enclos ...
, which allows them to migrate toward sites of infection or inflammation. Cell surface receptors allow neutrophils to detect chemical gradients of molecules such as
interleukin-8 Interleukin 8 (IL-8 or chemokine (C-X-C motif) ligand 8, CXCL8) is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells and endothelial cells. Endothelial cells Endothelium is a single ...
(IL-8),
interferon gamma Interferon gamma (IFNγ) is a protein dimer, dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F ...
(IFN-γ), C3a, C5a, and
Leukotriene B4 Leukotriene B4 (LTB4) is a leukotriene involved in inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a prote ...

Leukotriene B4
, which these cells use to direct the path of their migration. Neutrophils have a variety of specific receptors, including ones for
complement A complement is often something that completes something else, or at least adds to it in some useful way. Thus it may be: * Complement (linguistics), a word or phrase having a particular syntactic role ** Subject complement, a word or phrase addi ...

complement
, cytokines like
interleukin Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that were first seen to be expressed by white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the cells of the immune system ...
s and IFN-γ,
chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokine Cytokines are a broad and loose category of small protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the firs ...
s,
lectin Lectins are carbohydrate-binding proteins that are highly specific for sugar Moiety (chemistry), groups that are part of other molecules, so cause agglutination (biology), agglutination of particular cells or precipitation of Glycoconjugate, gly ...
s, and other proteins. They also express receptors to detect and adhere to
endothelium Endothelium is a single layer of squamous Epithelium () is one of the four basic types of animal Animals (also called Metazoa) are multicellular eukaryotic organisms that form the Kingdom (biology), biological kingdom Animalia. Wit ...
and
Fc receptor A Fc receptor is a protein found on the surface of certain cells – including, among others, B lymphocytes, follicular dendritic cells Follicular dendritic cells (FDC) are cells of the immune system The immune system is a network of ...
s for
opsonin Opsonins are proteins of the innate and adaptive immune system The adaptive immune system, also referred as the acquired immune system, is a subsystem of the immune system The immune system is a network of biological processes that protects an ...

opsonin
. In leukocytes responding to a
chemoattractant Chemotaxis (from '' chemo-'' + ''taxis A taxis (plural taxes , ) is the movement of an organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any individual contiguous system that embodies t ...
, the cellular polarity is regulated by activities of small
Rho Rho (uppercase Ρ, lowercase ρ or ; el, ῥῶ) is the 17th letter of the Greek alphabet The Greek alphabet has been used to write the Greek language since the late ninth or early eighth century BC. It is derived from the earlier Phoenician ...
guanosine triphosphatases ( Rho GTPases) and the
phosphoinositide 3-kinase Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon whi ...
s (
PI3K Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzyme Enzymes () are protein Proteins are large s and s that comprise one or more long chains of . Proteins perform a vast array of fun ...

PI3K
s). In neutrophils, lipid products of PI3Ks regulate activation of Rac1, hematopoietic Rac2, and RhoG GTPases of the Rho family and are required for
cell motility Motility is the ability of an organism In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecula ...
. Rac-GTPases regulate cytoskeletal dynamics and facilitate neutrophils adhesion, migration, and spreading. They accumulate asymmetrically to the
plasma membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane A biological membrane, biomembrane or cell membrane is a selectively permeable membra ...
at the leading edge of polarized cells. Spatially regulating Rho GTPases and organizing the leading edge of the cell, PI3Ks and their lipid products could play pivotal roles in establishing leukocyte polarity, as compass molecules that tell the cell where to crawl. It has been shown in mice that in certain conditions neutrophils have a specific type of migration behaviour referred to as neutrophil swarming during which they migrate in a highly coordinated manner and accumulate and cluster to sites of inflammation.


Anti-microbial function

Being highly
motile Motility is the ability of an organism to move independently, using metabolic energy. Definitions Motility, the ability of an organism to move independently, using metabolic energy, can be contrasted with Sessility (motility), sessility, the ...

motile
, neutrophils quickly congregate at a focus of
infection An infection is the invasion of an organism's body tissues by disease-causing agents, their multiplication, and the reaction of host A host is a person responsible for guests at an event or for providing hospitality during it. Host may ...

infection
, attracted by
cytokine Cytokines are a broad and loose category of small protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and ...

cytokine
s expressed by activated
endothelium Endothelium is a single layer of squamous Epithelium () is one of the four basic types of animal Animals (also called Metazoa) are multicellular eukaryotic organisms that form the Kingdom (biology), biological kingdom Animalia. Wit ...
,
mast cell#REDIRECT Mast cell A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem ...

mast cell
s, and
macrophage Macrophages (abbreviated as Mφ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the ...

macrophage
s. Neutrophils express and release cytokines, which in turn amplify inflammatory reactions by several other cell types. In addition to recruiting and activating other cells of the immune system, neutrophils play a key role in the front-line defense against invading pathogens. Neutrophils have three methods for directly attacking micro-organisms:
phagocytosis Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis Endocytosis is a cellular process i ...

phagocytosis
(ingestion),
degranulation 300px, The degranulation process in a Mast cell. 1 = FcεR1;_4_=_preformed_mediators_(histamine.html" ;"title="IgE;_3_=_FCER1.html" ;"title="IgE.html" ;"title="antigen; 2 = IgE">antigen; 2 = IgE; 3 = FCER1">FcεR1; 4 = preformed mediators (histamin ...
(release of soluble anti-microbials), and generation of
neutrophil extracellular traps File:Agregation of neutrophils around spontaneously activated netosis observed in Alzheimers' Desease patients blood.jpg, 250px, Fluorescent image of cultivated neutrophils isolated from venous blood of human with Alzheimer Disease. Sample was treat ...
(NETs).


Phagocytosis

Neutrophils are
phagocyte Phagocytes are cell (biology), cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or Apoptosis, dying cells. Their name comes from the Greek language, Greek ', "to eat" or "devour", and "-cyte", the suffix in ...
s, capable of ingesting microorganisms or particles. For targets to be recognized, they must be coated in
opsonin Opsonins are proteins of the innate and adaptive immune system The adaptive immune system, also referred as the acquired immune system, is a subsystem of the immune system The immune system is a network of biological processes that protects an ...

opsonin
s—a process known as
antibody opsonization Antibody opsonization is a process by which a pathogen is marked for destruction by antibody-dependent cellular cytotoxicity (ADCC), phagocytes, antibody-dependent cellular phagocytosis (ADCP), or complement-dependent cytotoxicity (CDC). Given no ...

antibody opsonization
. They can internalize and kill many
microbe A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes ...
s, each phagocytic event resulting in the formation of a
phagosome In cell biology Cell biology (also cellular biology or cytology) is a branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, M ...
into which
reactive oxygen species Reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from O2. Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen (O2) produce ...
and hydrolytic enzymes are secreted. The consumption of oxygen during the generation of reactive oxygen species has been termed the "
respiratory burst Respiratory burst (or oxidative burst) is the rapid release of the reactive oxygen species Reactive oxygen species (ROS) are highly chemicals formed from O2. Examples of ROS include s, , , , and . The reduction of molecular oxygen (O2) produce ...
", although unrelated to respiration or energy production. The respiratory burst involves the activation of the
enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates in ...

enzyme
NADPH oxidase NADPH Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle The Calvin cycle, light-independent reactions ...
, which produces large quantities of
superoxide A superoxide is a compound that contains the superoxide ion An ion () is an atom An atom is the smallest unit of ordinary matter In classical physics and general chemistry, matter is any substance that has mass and takes up space ...

superoxide
, a reactive oxygen species. Superoxide decays spontaneously or is broken down via enzymes known as
superoxide dismutase Superoxide dismutase (SOD, ) is an enzyme that alternately catalyzes the dismutation (or partitioning) of the superoxide () radical (chemistry), radical into ordinary molecular oxygen (O2) and hydrogen peroxide (). Superoxide is produced as a by-p ...
s (Cu/ZnSOD and MnSOD), to hydrogen peroxide, which is then converted to
hypochlorous acid Hypochlorous acid (HOCl or HClO) is a weak acid An acid is a molecule or ion capable of donating a proton (hydrogen ion H+) (a Brønsted–Lowry acid–base theory, Brønsted–Lowry acid), or, alternatively, capable of forming a covalent bo ...
(HClO), by the green heme enzyme
myeloperoxidase Myeloperoxidase (MPO) is a peroxidase Peroxidases or peroxide reductases ( EC numberbr>1.11.1.x are a large group of enzyme Enzymes () are protein Proteins are large s and s that comprise one or more long chains of . Proteins per ...

myeloperoxidase
. It is thought that the bactericidal properties of HClO are enough to kill bacteria phagocytosed by the neutrophil, but this may instead be a step necessary for the activation of proteases. Though neutrophils can kill many microbes, the interaction of neutrophils with microbes and molecules produced by microbes often alters neutrophil turnover. The ability of microbes to alter the fate of neutrophils is highly varied, can be microbe-specific, and ranges from prolonging the neutrophil lifespan to causing rapid neutrophil lysis after phagocytosis. ''
Chlamydia pneumoniae ''Chlamydia pneumoniae'' is a species of ''Chlamydia (genus), Chlamydia'', an Obligate intracellular parasite, obligate intracellular bacterium that infects humans and is a major cause of pneumonia. It was known as the Taiwan acute respiratory ag ...

Chlamydia pneumoniae
'' and ''
Neisseria gonorrhoeae ''Neisseria gonorrhoeae'', also known as ''gonococcus'' (singular), or ''gonococci'' (plural), is a species of Gram-negative diplococci bacteria isolated by Albert Ludwig Sigesmund Neisser, Albert Neisser in 1879. It causes the sexually transmit ...

Neisseria gonorrhoeae
'' have been reported to delay neutrophil apoptosis. Thus, some bacteria—and those that are predominantly intracellular pathogens—can extend the neutrophil lifespan by disrupting the normal process of spontaneous apoptosis and/or PICD (phagocytosis-induced cell death). On the other end of the spectrum, some pathogens such as ''
Streptococcus pyogenes ''Streptococcus pyogenes'' is a species In biology, a species is the basic unit of biological classification, classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest gr ...

Streptococcus pyogenes
'' are capable of altering neutrophil fate after phagocytosis by promoting rapid cell lysis and/or accelerating apoptosis to the point of secondary necrosis. Material was copied from this source, which is available under
Creative Commons Attribution 4.0 International License


Degranulation

Neutrophils also release an assortment of proteins in three types of granules by a process called
degranulation 300px, The degranulation process in a Mast cell. 1 = FcεR1;_4_=_preformed_mediators_(histamine.html" ;"title="IgE;_3_=_FCER1.html" ;"title="IgE.html" ;"title="antigen; 2 = IgE">antigen; 2 = IgE; 3 = FCER1">FcεR1; 4 = preformed mediators (histamin ...
. The contents of these granules have antimicrobial properties, and help combat infection.


Neutrophil extracellular traps

In 2004, Brinkmann and colleagues described a striking observation that activation of neutrophils causes the release of web-like structures of DNA; this represents a third mechanism for killing bacteria. These
neutrophil extracellular traps File:Agregation of neutrophils around spontaneously activated netosis observed in Alzheimers' Desease patients blood.jpg, 250px, Fluorescent image of cultivated neutrophils isolated from venous blood of human with Alzheimer Disease. Sample was treat ...
(NETs) comprise a web of fibers composed of
chromatin Chromatin is a complex of DNA Deoxyribonucleic acid (; DNA) is a molecule File:Pentacene on Ni(111) STM.jpg, A scanning tunneling microscopy image of pentacene molecules, which consist of linear chains of five carbon rings. A molecu ...
and
serine protease Serine proteases (or serine endopeptidases) are enzyme Enzymes () are protein Proteins are large s and s that comprise one or more long chains of . Proteins perform a vast array of functions within organisms, including , , , provi ...

serine protease
s that trap and kill extracellular microbes. It is suggested that NETs provide a high local concentration of antimicrobial components and bind, disarm, and kill microbes independent of phagocytic uptake. In addition to their possible antimicrobial properties, NETs may serve as a physical barrier that prevents further spread of pathogens. Trapping of bacteria may be a particularly important role for NETs in
sepsis Sepsis is a life-threatening condition that arises when the body's response to infection An infection is the invasion of an organism's body by , their multiplication, and the reaction of tissues to the infectious agents and the s they pr ...
, where NETs are formed within blood vessels. Finally, NET formation has been demonstrated to augment macrophage bactericidal activity during infection. Recently, NETs have been shown to play a role in inflammatory diseases, as NETs could be detected in
preeclampsia Pre-eclampsia is a disorder of pregnancy characterized by the onset of high blood pressure Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term Disease, medical condition in which the blood pressure in the arter ...
, a pregnancy-related inflammatory disorder in which neutrophils are known to be activated. Neutrophil NET formation may also impact
cardiovascular disease Cardiovascular disease (CVD) is a class of diseases that involve the heart The heart is a cardiac muscle, muscular Organ (biology), organ in most animals, which pumps blood through the blood vessels of the circulatory system. The pumped ...
, as NETs may influence
thrombus A thrombus, colloquially called a blood clot, is the final product of the blood coagulation Coagulation, also known as clotting, is the process by which blood Blood is a body fluid in humans and other animals that delivers necessary sub ...
formation in coronary arteries. NETs are now known to exhibit pro-Thrombosis, thrombotic effects both ''in vitro'' and ''in vivo''.


Clinical significance

Low neutrophil counts are termed ''neutropenia''. This can be congenital disorder, congenital (developed at or before birth) or it can develop later, as in the case of aplastic anemia or some kinds of leukemia. It can also be a adverse effect (medicine), side-effect of medication, most prominently chemotherapy. Neutropenia makes an individual highly susceptible to infections. It can also be the result of colonization by intracellular neutrophilic parasites. In alpha 1-antitrypsin deficiency, the important neutrophil elastase is not adequately inhibited by alpha 1-antitrypsin, leading to excessive tissue damage in the presence of inflammation – the most prominent one being emphysema. Negative effects of elastase has been also shown in cases when the neutrophils are excessively activated (in otherwise healthy individual) and release the enzyme in extracellular space. Unregulated activity of neutrophil elastase can lead to disruption of pulmonary barrier showing symptoms corresponding with Acute respiratory distress syndrome, acute lung injury. The enzyme also influences activity of macrophages by cleaving their toll-like receptors (TLRs) and downregulating
cytokine Cytokines are a broad and loose category of small protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and ...

cytokine
expression by inhibiting nuclear translocation of NF-κB. In Familial Mediterranean fever (FMF), a mutation in the ''pyrin'' (or ''marenostrin'') gene, which is expressed mainly in neutrophil granulocytes, leads to a constitutively active acute-phase protein, acute-phase response and causes attacks of fever, arthralgia, peritonitis, and – eventually – amyloidosis. Decreases in neutrophil function have been linked to hyperglycemia. Dysfunction in the neutrophil biochemical pathway
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myeloperoxidase
as well as reduced degranulation are associated with hyperglycemia. The Absolute neutrophil count (ANC) is also used in diagnosis and prognosis. ANC is the gold standard for determining severity of neutropenia, and thus neutropenic fever. Any ANC < 1500 cells / mm3 is considered neutropenia, but <500 cells / mm3 is considered severe. There is also new research tying ANC to myocardial infarction as an aid in early diagnosis. In autopsy, the presence of neutrophils in the heart or brain is one of the first signs of infarction, and is therefore useful the myocardial infarction diagnosis, diagnosis of myocardial infarction and stroke, and the timing thereof. File:Histopathology of neutrophil infiltration in myocardial infarction.jpg, Neutrophils are seen in a myocardial infarction at approximately 12–24 hours,
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as seen in this micrograph. File:Histopathology of thalamus infarction at approximately 24 hours, high magnification, annotated.jpg, In stroke, they are beginning to infiltrate the infarcted brain after 6 to 8 hours.


Neutrophil antigens

There are five (HNA 1–5) sets of neutrophil antigens recognized. The three HNA-1 antigens (a-c) are located on the low affinity Fc-γ receptor IIIb (FCGR3B :CD16b) The single known HNA-2a antigen is located on CD177. The HNA-3 antigen system has two antigens (3a and 3b) which are located on the seventh exon of the CLT2 gene (SLC44A2). The HNA-4 and HNA-5 antigen systems each have two known antigens (a and b) and are located in the β2
integrin Integrins are transmembrane receptors Cell surface receptors (membrane receptors, transmembrane receptors) are receptor (biochemistry), receptors that are embedded in the cell membrane, plasma membrane of cell (biology), cells. They act in cell ...

integrin
. HNA-4 is located on the αM chain (CD11b) and HNA-5 is located on the αL integrin unit (CD11a).


Subpopulations

Two functionally unequal subpopulations of neutrophils were identified on the basis of different levels of their reactive oxygen metabolite generation, membrane permeability, activity of enzyme system, and ability to be inactivated. The cells of one subpopulation with high membrane permeability (neutrophil-killers) intensively generate reactive oxygen metabolites and are inactivated in consequence of interaction with the substrate, whereas cells of another subpopulation (neutrophil-cagers) produce reactive oxygen species less intensively, don't adhere to substrate and preserve their activity. Additional studies have shown that lung tumors can be infiltrated by various populations of neutrophils.


Video

File:S1-Polymorphonuclear Cells with Conidia in Liquid Media.ogv, A rapidly moving neutrophil can be seen taking up several conidia over an imaging time of 2 hours with one frame every 30 seconds. File:S15-Competitive Phagocytosis Assay in Collagen.ogg, A neutrophil can be seen here selectively taking up several Candida (genus), ''Candida'' yeasts (Fluorescent labelling, fluorescently labeled in green) despite several contacts with ''Aspergillus fumigatus'' conidia (unlabeled, white/clear) in a 3-D collagen matrix. Imaging time was 2 hours with one frame every 30 seconds. Neutrophils display highly directional amoeboid motility in infected footpad and phalanges. Intravital imaging was performed in the footpad path of LysM-eGFP mice 20 minutes after infection with ''Listeria monocytogenes''.


Additional images

File:Illu blood cell lineage.jpg, Blood cell lineage File:Hematopoiesis (human) diagram en.svg, More complete lineages


References


External links


Neutropenia InformationAbsolute Neutrophil Count CalculatorNeutrophil Trace Element Content and Distribution
{{DEFAULTSORT:Neutrophil Granulocyte Cell biology Granulocytes Phagocytes Human cells Articles containing video clips