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 evolutionary defense strategy, relatively speaking, and is the ...

characterized by the presence of

specific granule Specific granules are secretory vesicles found exclusively in cells of the immune system called granulocytes. It is sometimes described as applying specifically to neutrophils, and sometimes the term is applied to other types of cells. These gra ...

s in their

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...

. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear. They have varying shapes (morphology) of the

nucleus Nucleus ( : 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 Nucl ...

(segmented, irregular; often lobed into three segments); and are referred to as polymorphonuclear leukocytes (PMN, PML, or PMNL). In common terms, ''polymorphonuclear granulocyte'' refers specifically to "

neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...

granulocytes", the most abundant of the granulocytes; the other types (

eosinophil Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...

basophil Basophils are a type of 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 responsible for inflammator ...

s, and mast cells) have varying morphology. Granulocytes are produced via granulopoiesis in the

bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...

Types

There are four types of granulocytes (full name polymorphonuclear granulocytes): *

Basophil Basophils are a type of 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 responsible for inflammator ...

s *

Eosinophil Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...

s *

Neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...

s * Mast cells Except for the mast cells, their names are derived from their

staining Staining is a technique used to enhance contrast in samples, generally at the microscopic level. Stains and dyes are frequently used in histology (microscopic study of biological tissues), in cytology (microscopic study of cells), and in th ...

characteristics; for example, the most abundant granulocyte is the

neutrophil granulocyte Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...

, which has neutrally staining

ic granules.

Neutrophils

Neutrophils are normally found in the

bloodstream The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...

and are the most abundant type of

phagocyte Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek ', "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek ...

, constituting 60% to 65% of the total circulating white blood cells, and consisting of two subpopulations: neutrophil-killers and neutrophil-cagers. One litre of human blood contains about five billion (5x10⁹) neutrophils,Hoffbrand p. 331 which are about 12–15

micrometre The micrometre (American and British English spelling differences#-re, -er, international spelling as used by the International Bureau of Weights and Measures; SI symbol: μm) or micrometer (American and British English spelling differences# ...

s in diameter.Abbas, Chapter 12, 5th Edition Once neutrophils have received the appropriate signals, it takes them about thirty minutes to leave the blood and reach the site of an infection.Sompayrac p. 18 Neutrophils do not return to the blood; they turn into pus cells and die. Mature neutrophils are smaller than monocytes, and have a segmented

with several sections(two to five segments); each section is connected by

chromatin Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important ...

filaments. Neutrophils do not normally exit the bone marrow until maturity, but during an infection neutrophil precursors called

myelocyte A myelocyte is a young cell of the granulocytic series, occurring normally in bone marrow (can be found in circulating blood when caused by certain diseases). Structure When stained with the usual dyes, the cytoplasm is distinctly basophil ...

s and promyelocytes are released. Neutrophils have three strategies 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. A cell that performs phagocytosis is ...

(ingestion), release of soluble anti-microbials (including granule proteins), and generation of

neutrophil extracellular traps Neutrophil extracellular traps (NETs) are networks of extracellular fibers, primarily composed of DNA from neutrophils, which bind pathogens. Neutrophils are the immune system's first line of defense against infection and have conventionally ...

(NETs). Neutrophils are professional phagocytes:Robinson p. 187 and Ernst pp. 7–10 they are ferocious eaters and rapidly engulf invaders coated with

antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of ...

and complement, as well as damaged cells or cellular debris. The intracellular granules of the human neutrophil have long been recognized for their protein-destroying and bactericidal properties. Neutrophils can secrete products that stimulate monocytes and

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

s; these secretions increase phagocytosis and the formation of reactive oxygen compounds involved in intracellular killing. Neutrophils have two types of granules; primary (azurophilic) granules (found in young cells) and secondary (specific) granules (which are found in more mature cells). Primary granules contain cationic proteins and

defensin Defensins are small cysteine-rich cationic proteins across cellular life, including vertebrate and invertebrate animals, plants, and fungi. They are host defense peptides, with members displaying either direct antimicrobial activity, immune ...

s that are used to kill bacteria, proteolytic enzymes and cathepsin G to break down (bacterial) proteins, lysozyme to break down bacterial

cell walls A cell wall is a structural layer surrounding some types of cells, just outside the cell membrane. It can be tough, flexible, and sometimes rigid. It provides the cell with both structural support and protection, and also acts as a filtering mech ...

, and myeloperoxidase (used to generate toxic bacteria-killing substances). In addition, secretions from the primary granules of neutrophils stimulate the phagocytosis of

IgG Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG an ...

antibody-coated bacteria. The secondary granules contain compounds that are involved in the formation of toxic oxygen compounds, lysozyme, and

lactoferrin Lactoferrin (LF), also known as lactotransferrin (LTF), is a multifunctional protein of the transferrin family. Lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa that is widely represented in various secretory fluids, s ...

(used to take essential

iron Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in ...

from bacteria).

Neutrophil extracellular traps Neutrophil extracellular traps (NETs) are networks of extracellular fibers, primarily composed of DNA from neutrophils, which bind pathogens. Neutrophils are the immune system's first line of defense against infection and have conventionally ...

(NETs) comprise a web of fibers composed of

and

serine protease Serine proteases (or serine endopeptidases) are enzymes that cleave peptide bonds in proteins. Serine serves as the nucleophilic amino acid at the (enzyme's) active site. They are found ubiquitously in both eukaryotes and prokaryotes. Seri ...

s that trap and kill microbes extracellularly. Trapping of bacteria is a particularly important role for NETs in sepsis, where NET are formed within blood vessels.

Eosinophils

Eosinophils also have kidney-shaped

lobed The following is a list of terms which are used to describe leaf morphology in the description and taxonomy of plants. Leaves may be simple (a single leaf blade or lamina) or compound (with several leaflets). The edge of the leaf may be regular o ...

nuclei (two to four lobes). The number of granules in an eosinophil can vary because they have a tendency to degranulate while in the blood stream. Eosinophils play a crucial part in the killing of parasites (e.g., enteric nematodes) because their granules contain a unique, toxic basic protein and cationic protein (e.g., cathepsin); receptors that bind to

and

IgA Iga may refer to: Arts and entertainment * Ambush at Iga Pass, a 1958 Japanese film * Iga no Kagemaru, Japanese manga series * Iga, a set of characters from the Japanese novel '' The Kouga Ninja Scrolls'' Biology * ''Iga'' (beetle), a g ...

are used to help with this task. These cells also have a limited ability to participate in phagocytosis,Campbell p. 903 they are professional antigen-presenting cells, they regulate other immune cell functions (e.g., CD4+ T cell,

dendritic cell Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. Th ...

B cell B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted o ...

, mast cell,

, and

functions), they are involved in the destruction of tumor cells, and they promote the repair of damaged tissue. A polypeptide called interleukin-5 interacts with eosinophils and causes them to grow and differentiate; this polypeptide is produced by basophils and by T-helper 2 cells (TH2).

Basophils

Basophils are one of the least abundant cells in

and

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...

(occurring at less than two percent of all cells). Like neutrophils and eosinophils, they have lobed nuclei; however, they have only two lobes, and the

filaments that connect them are not very visible. Basophils have receptors that can bind to IgE,

, complement, and

histamine Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discover ...

. The

of basophils contains a varied amount of granules; these granules are usually numerous enough to partially conceal the nucleus. Granule contents of basophils are abundant with histamine,

heparin Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the treat ...

chondroitin sulfate Chondroitin sulfate is a sulfated glycosaminoglycan (GAG) composed of a chain of alternating sugars ( N-acetylgalactosamine and glucuronic acid). It is usually found attached to proteins as part of a proteoglycan. A chondroitin chain can have ove ...

, peroxidase, platelet-activating factor, and other substances. When an infection occurs, mature basophils will be released from the bone marrow and travel to the site of infection. When basophils are injured, they will release histamine, which contributes to the inflammatory response that helps fight invading organisms. Histamine causes dilation and increased permeability of

capillaries A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...

close to the basophil. Injured basophils and other

leukocytes White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mu ...

will release another substance called

prostaglandins The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are deri ...

that contributes to an increased blood flow to the site of infection. Both of these mechanisms allow blood-clotting elements to be delivered to the infected area (this begins the recovery process and blocks the travel of microbes to other parts of the body). Increased permeability of the inflamed tissue also allows for more

migration to the site of infection so that they can consume microbes.

Mast cells

Mast cells are a type of granulocyte that are present in tissues; they mediate host defense against

pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a g ...

s (e.g.,

parasite Parasitism is a close relationship between species, where one organism, the parasite, lives on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The entomologist E. O. Wilson h ...

s) and

allergic reaction Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derm ...

s, particularly

anaphylaxis Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follo ...

. Mast cells are also involved in mediating

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 protective response involving immune cells, blood vessels, and molec ...

and

autoimmunity In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". ...

as well as mediating and regulating neuroimmune system responses.

Development

Granulocytes are derived from stem cells residing in the bone marrow. The differentiation of these stem cells from pluripotent

hematopoietic stem cell Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the very first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within ...

into granulocytes is termed granulopoiesis. Multiple intermediate cell types exist in this differentiation process, including

myeloblasts The myeloblast is a unipotent stem cell which differentiates into the effectors of the granulocyte series. It is found in the bone marrow. Stimulation of myeloblasts by G-CSF and other cytokines triggers maturation, differentiation, proliferation ...

and promyelocytes.

Function

Granule contents

Examples of toxic materials produced or released by

degranulation Degranulation is a cellular process that releases antimicrobial cytotoxic or other molecules from secretory vesicles called granules found inside some cells. It is used by several different cells involved in the immune system, including gra ...

by granulocytes on the ingestion of microorganisms are: *

Antimicrobial An antimicrobial is an agent that kills microorganisms or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals ar ...

agents (

Defensin Defensins are small cysteine-rich cationic proteins across cellular life, including vertebrate and invertebrate animals, plants, and fungi. They are host defense peptides, with members displaying either direct antimicrobial activity, immune ...

s and

Eosinophil cationic protein Eosinophil cationic protein (ECP) also known as ribonuclease 3 is a basic protein located in the eosinophil primary matrix. In humans, the eosinophil cationic protein is encoded by the ''RNASE3'' gene. ECP is released during degranulation of eosi ...

) *

Enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

s **

Acid hydrolase An acid hydrolase is an enzyme that works best at acidic pHs. It is commonly located in lysosomes, which are acidic on the inside. Acid hydrolases may be nucleases, proteases, glycosidases, lipases, phosphatases, sulfatases and phospholipas ...

s: further digest bacteria **

Lysozyme Lysozyme (EC 3.2.1.17, muramidase, ''N''-acetylmuramide glycanhydrolase; systematic name peptidoglycan ''N''-acetylmuramoylhydrolase) is an antimicrobial enzyme produced by animals that forms part of the innate immune system. It is a glycoside ...

: dissolves cell walls of some

gram-positive bacteria In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bac ...

* Low pH

vesicles Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features o ...

(3.5-4.0) * Toxic

nitrogen Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at se ...

oxides (

nitric oxide Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its ...

) * Toxic

oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements ...

-derived products (e.g.,

superoxide In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formula . The systematic name of the anion is dioxide(1−). The reactive oxygen ion superoxide is particularly important as the product of t ...

hydrogen peroxide Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3 ...

hydroxy radical The hydroxyl radical is the diatomic molecule . The hydroxyl radical is very stable as a dilute gas, but it decays very rapidly in the condensed phase. It is pervasive in some situations. Most notably the hydroxyl radicals are produced from the ...

singlet oxygen Singlet oxygen, systematically named dioxygen(singlet) and dioxidene, is a gaseous inorganic chemical with the formula O=O (also written as or ), which is in a quantum state where all electrons are spin paired. It is kinetically unstable at ambi ...

, hypohalite)

Clinical significance

Granulocytopenia is an abnormally low concentration of granulocytes in the blood. This condition reduces the body's resistance to many infections. Closely related terms include

agranulocytosis Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous lowered white blood cell count (leukopenia, most commonly of neutrophils) and thus causing a neutropenia in the circulating blood. ...

(etymologically, "no granulocytes at all"; clinically, granulocyte levels less than 5% of normal) and

neutropenia Neutropenia is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteri ...

(deficiency of

s). Granulocytes live only one to two days in circulation (four days in

spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .

or other tissue), so transfusion of granulocytes as a therapeutic strategy would confer a very short-lasting benefit. In addition, there are many complications associated with such a procedure. There is usually a granulocyte chemotactic defect in individuals suffering from

type 1 diabetes mellitus Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar f ...

. Research suggests giving granulocyte transfusions to prevent infections decreased the number of people who had a bacterial or fungal infection in the blood. Further research suggests participants receiving therapeutic granulocyte transfusions show no difference in clinical reversal of concurrent infection.

Additional images

Image:Hematopoiesis (human) diagram en.svg, Hematopoiesis

References

Bibliography

* * * * * * *

External links

* {{Authority control Leukocytes