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Phagocytosis () is the process by which a cell uses its
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 that separates and protects the interior of all cells from the outside environment (t ...
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 in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. ...
. A cell that performs phagocytosis is called a phagocyte. In a multicellular organism's
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
, phagocytosis is a major mechanism used to remove
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 and cell debris. The ingested material is then digested in the phagosome. Bacteria, dead tissue cells, and small mineral particles are all examples of objects that may be phagocytized. Some
protozoa Protozoa (singular: protozoan or protozoon; alternative plural: protozoans) are a group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic tissues and debris. Histo ...
use phagocytosis as means to obtain nutrients.


History

Phagocytosis was first noted by Canadian physician
William Osler Sir William Osler, 1st Baronet, (; July 12, 1849 – December 29, 1919) was a Canadian physician and one of the "Big Four" founding professors of Johns Hopkins Hospital. Osler created the first residency program for specialty training of phys ...
(1876), and later studied and named by
Élie Metchnikoff Ilya Ilyich Mechnikov (russian: Илья Ильич Мечников; – 15 July 1916), also spelled Élie Metchnikoff, was a Russian zoologist best known for his pioneering research in immunology. Belkin, a Russian science historian, explain ...
(1880, 1883).


In immune system

Phagocytosis is one main mechanisms of the innate immune defense. It is one of the first processes responding to
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...
, and is also one of the initiating branches of an adaptive immune response. Although most cells are capable of phagocytosis, some cell types perform it as part of their main function. These are called 'professional phagocytes.' Phagocytosis is old in evolutionary terms, being present even in
invertebrate Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chorda ...
s.


Professional phagocytic cells

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,
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,
monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also ...
s,
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 ...
s, osteoclasts and eosinophils can be classified as professional phagocytes. The first three have the greatest role in immune response to most infections. The role of neutrophils is patrolling the bloodstream and rapid migration to the tissues in large numbers only in case of infection. There they have direct microbicidal effect by phagocytosis. After ingestion, neutrophils are efficient in intracellular killing of pathogens. Neutrophils phagocytose mainly via the Fcγ receptors and complement receptors 1 and 3. The microbicidal effect of neutrophils is due to a large repertoire of molecules present in pre-formed granules. Enzymes and other molecules prepared in these granules are proteases, such as collagenase, gelatinase or
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, myeloperoxidase, lactoferrin and antibiotic proteins. Degranulation of these into the phagosome, accompanied by high reactive oxygen species production (oxidative burst) is highly microbicidal. Monocytes, and the macrophages that mature from them, leave blood circulation to migrate through tissues. There they are resident cells and form a resting barrier. Macrophages initiate phagocytosis by mannose receptors, scavenger receptors, Fcγ receptors and complement receptors 1, 3 and 4. Macrophages are long-lived and can continue phagocytosis by forming new lysosomes. Dendritic cells also reside in tissues and ingest pathogens by phagocytosis. Their role is not killing or clearance of microbes, but rather breaking them down for
antigen presentation Antigen presentation is a vital immune process that is essential for T cell immune response triggering. Because T cells recognize only fragmented antigens displayed on cell surfaces, antigen processing must occur before the antigen fragment, n ...
to the cells of the adaptive immune system.


Initiating receptors

Receptors for phagocytosis can be divided into two categories by recognised molecules. The first, opsonic receptors, are dependent on opsonins. Among these are receptors that recognise the Fc part of bound
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 ...
antibodies, deposited complement or receptors, that recognise other opsonins of cell or plasma origin. Non-opsonic receptors include lectin-type receptors, Dectin receptor, or scavenger receptors. Some phagocytic pathways require a second signal from
pattern recognition receptor Pattern recognition receptors (PRRs) play a crucial role in the proper function of the innate immune system. PRRs are germline-encoded host sensors, which detect molecules typical for the pathogens. They are proteins expressed, mainly, by cells of ...
s (PRRs) activated by attachment to pathogen-associated molecular patterns (PAMPS), which leads to NF-κB activation.


Fcγ receptors

Fcγ receptors recognise IgG coated targets. The main recognised part is the
Fc fragment The fragment crystallizable region (Fc region) is the tail region of an antibody that interacts with cell surface receptors called Fc receptors and some proteins of the complement system. This property allows antibodies to activate the immune ...
. The molecule of the receptor contain an intracellular ITAM domain or associates with an ITAM-containing adaptor molecule. ITAM domains transduce the signal from the surface of the phagocyte to the nucleus. For example, activating receptors of human macrophages are FcγRI, FcγRIIA, and FcγRIII. Fcγ receptor mediated phagocytosis includes formation of protrusions of the cell called a 'phagocytic cup' and activates an oxidative burst in neutrophils.


Complement receptors

These receptors recognise targets coated in
C3b C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the innate immune system. C3b is potent in opsonization: tagging pathogens, immune complexes (antigen-antibody), and apoptot ...
, C4b and C3bi from plasma complement. The extracellular domain of the receptors contains a lectin-like complement-binding domain. Recognition by complement receptors is not enough to cause internalisation without additional signals. In macrophages, the CR1, CR3 and CR4 are responsible for recognition of targets. Complement coated targets are internalised by 'sinking' into the phagocyte membrane, without any protrusions.


Mannose receptors

Mannose Mannose is a sugar monomer of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylation of certain proteins. Several congenital disorders of glycosylat ...
and other pathogen-associated sugars, such as fucose, are recognised by the mannose receptor. Eight lectin-like domains form the extracellular part of the receptor. The ingestion mediated by the mannose receptor is distinct in molecular mechanisms from Fcγ receptor or complement receptor mediated phagocytosis.


Phagosome

Engulfment of material is facilitated by the actin-myosin contractile system. The phagosome is the organelle formed by phagocytosis of material. It then moves toward the centrosome of the phagocyte and is fused with
lysosome A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane p ...
s, forming a phagolysosome and leading to degradation. Progressively, the phagolysosome is acidified, activating degradative enzymes. Degradation can be oxygen-dependent or oxygen-independent. * Oxygen-dependent degradation depends on
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 and lipid and nucleic acid syntheses, which require NA ...
and the production of reactive oxygen species.
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 ...
and myeloperoxidase activate a halogenating system, which leads to the creation of
hypochlorite In chemistry, hypochlorite is an anion with the chemical formula ClO−. It combines with a number of cations to form hypochlorite salts. Common examples include sodium hypochlorite (household bleach) and calcium hypochlorite (a component of ...
and the destruction of bacteria. * Oxygen-independent degradation depends on the release of granules, containing enzymes such as lysozymes, and cationic proteins such as
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. Other antimicrobial peptides are present in these granules, including lactoferrin, which sequesters
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 ...
to provide unfavourable growth conditions for bacteria. Other enzymes like hyaluronidase, lipase, collagenase, elastase, ribonuclease, deoxyribonuclease also play an important role in preventing the spread of infection and degradation of essential microbial biomolecules leading to cell death.
Leukocyte 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 mult ...
s generate
hydrogen cyanide Hydrogen cyanide, sometimes called prussic acid, is a chemical compound with the formula HCN and structure . It is a colorless, extremely poisonous, and flammable liquid that boils slightly above room temperature, at . HCN is produced on a ...
during phagocytosis, and can kill
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...
,
fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately fr ...
, and other pathogens by generating several other toxic chemicals. Some bacteria, for example ''
Treponema pallidum ''Treponema pallidum'', formerly known as ''Spirochaeta pallida'', is a spirochaete bacterium with various subspecies that cause the diseases syphilis, bejel (also known as endemic syphilis), and yaws. It is transmitted only among humans. It is ...
'', ''
Escheria coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Esche ...
'' and ''
Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posit ...
'', are able to avoid phagocytosis by several mechanisms.


In apoptosis

Following
apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes in ...
, the dying cells need to be taken up into the surrounding tissues by macrophages in a process called
efferocytosis In cell biology, efferocytosis (from ''efferre'', Latin for 'to take to the grave', 'to bury') is the process by which apoptotic cells are removed by phagocytic cells. It can be regarded as the 'burying of dead cells'. During efferocytosis, the cel ...
. One of the features of an apoptotic cell is the presentation of a variety of intracellular molecules on the cell surface, such as calreticulin, phosphatidylserine (from the inner layer of the plasma membrane), annexin A1, oxidised LDL and altered glycans. These molecules are recognised by receptors on the cell surface of the macrophage such as the phosphatidylserine receptor or by soluble (free-floating) receptors such as thrombospondin 1, GAS6, and
MFGE8 Milk fat globule-EGF factor 8 protein (Mfge8), also known as lactadherin, is a protein that in humans is encoded by the ''MFGE8'' gene. Species distribution Mfge8 is a secreted protein found in vertebrates, including mammals as well as birds. ...
, which themselves then bind to other receptors on the macrophage such as CD36 and alpha-v beta-3 integrin. Defects in apoptotic cell clearance is usually associated with impaired phagocytosis of macrophages. Accumulation of apoptotic cell remnants often causes autoimmune disorders; thus pharmacological potentiation of phagocytosis has a medical potential in treatment of certain forms of autoimmune disorders.


In protists

In many
protist A protist () is any eukaryotic organism (that is, an organism whose cells contain a cell nucleus) that is not an animal, plant, or fungus. While it is likely that protists share a common ancestor (the last eukaryotic common ancestor), the e ...
s, phagocytosis is used as a means of feeding, providing part or all of their nourishment. This is called phagotrophic nutrition, distinguished from osmotrophic nutrition which takes place by absorption. * In some, such as
amoeba An amoeba (; less commonly spelled ameba or amœba; plural ''am(o)ebas'' or ''am(o)ebae'' ), often called an amoeboid, is a type of cell or unicellular organism with the ability to alter its shape, primarily by extending and retracting pseudop ...
, phagocytosis takes place by surrounding the target object with pseudopods, as in animal phagocytes. In humans, the amoebozoan ''
Entamoeba histolytica ''Entamoeba histolytica'' is an anaerobic parasitic amoebozoan, part of the genus ''Entamoeba''. Predominantly infecting humans and other primates causing amoebiasis, ''E. histolytica'' is estimated to infect about 35-50 million people worldwid ...
'' can phagocytose
red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "hol ...
s. *
Ciliate The ciliates are a group of alveolates characterized by the presence of hair-like organelles called cilia, which are identical in structure to eukaryotic flagella, but are in general shorter and present in much larger numbers, with a differen ...
s also engage in phagocytosis. In ciliates there is a specialized groove or chamber in the cell where phagocytosis takes place, called the
cytostome A cytostome (from ''cyto-'', cell and ''stome-'', mouth) or cell mouth is a part of a cell specialized for phagocytosis, usually in the form of a microtubule-supported funnel or groove. Food is directed into the cytostome, and sealed into vacuole ...
or mouth. As in phagocytic immune cells, the resulting phagosome may be merged with lysosomes( food vacuoles) containing digestive
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, forming a phagolysosome. The food particles will then be digested, and the released nutrients are diffused or transported into the cytosol for use in other metabolic processes.
Mixotrophy A mixotroph is an organism that can use a mix of different sources of energy and carbon, instead of having a single trophic mode on the continuum from complete autotrophy at one end to heterotrophy at the other. It is estimated that mixotrophs comp ...
can involve phagotrophic nutrition and phototrophic nutrition.


See also

* Active transport *
Antigen presentation Antigen presentation is a vital immune process that is essential for T cell immune response triggering. Because T cells recognize only fragmented antigens displayed on cell surfaces, antigen processing must occur before the antigen fragment, n ...
*
Antigen-presenting cell An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes usi ...
*
Emperipolesis Emperipolesis is the presence of an intact cell within the cytoplasm of another cell. It is derived from Greek (''en'' is ''inside'', ''peripoleomai'' is ''go round'').Emperipolesis. Stedman's Medical Dictionary. 27th Ed. Emperipolesis is an uncomm ...
* Endosymbionts in protists *
Paracytophagy Paracytophagy () is the cellular process whereby a cell engulfs a protrusion which extends from a neighboring cell. This protrusion may contain material which is actively transferred between the cells. The process of paracytophagy was first descr ...
*
Phagoptosis Phagoptosis is a type of cell death caused by the cell being phagocytosed (i.e. eaten) by another cell, and therefore this form of cell death is prevented by blocking phagocytosis. Phagocytosis of an otherwise-viable cell may occur because the cell ...
* Pinocytosis * Residual body *
Cell wall 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 mec ...


References


External links

* * {{Authority control Cellular processes Articles containing video clips Phagocytes