Phagocytosis

Last updated
Overview of phagocytosis 0309 Phagocytosis.png
Overview of phagocytosis
Phagocytosis versus exocytosis Phagocytosis and Exocytosis.svg
Phagocytosis versus exocytosis

Phagocytosis (from Ancient Greek φαγεῖν(phagein) 'to eat',andκύτος, (kytos) 'cell') 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 called a phagocyte.

Contents

The engulfing of a pathogen by a phagocyte Process of Phagocytosis.svg
The engulfing of a pathogen by a phagocyte

In a multicellular organism's immune system, phagocytosis is a major mechanism used to remove pathogens 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 use phagocytosis as means to obtain nutrients.

History

Phagocytosis was first noted by Canadian physician William Osler (1876), [1] and later studied and named by Élie Metchnikoff (1880, 1883). [2]

In immune system

Scanning electron micrograph of a phagocyte (yellow, right) phagocytosing anthrax bacilli (orange, left) Neutrophil with anthrax copy.jpg
Scanning electron micrograph of a phagocyte (yellow, right) phagocytosing anthrax bacilli (orange, left)

Phagocytosis is one main mechanisms of the innate immune defense. It is one of the first processes responding to infection, 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 invertebrates. [3]

Professional phagocytic cells

Light microscopic video sequence of a neutrophil from human blood phagocytosing a bacterium

Neutrophils, macrophages, monocytes, dendritic cells, osteoclasts and eosinophils can be classified as professional phagocytes. [2] The first three have the greatest role in immune response to most infections. [3]

The role of neutrophils is patrolling the bloodstream and rapid migration to the tissues in large numbers only in case of infection. [3] 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 proteases, myeloperoxidase, lactoferrin and antibiotic proteins. Degranulation of these into the phagosome, accompanied by high reactive oxygen species production (oxidative burst) is highly microbicidal. [4]

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. [3] 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. [3] [5]

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 to the cells of the adaptive immune system. [3]

Initiating receptors

Receptors for phagocytosis can be divided into two categories by recognised molecules. The first, opsonic receptors, are dependent on opsonins. [6] Among these are receptors that recognise the Fc part of bound IgG 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 receptors (PRRs) activated by attachment to pathogen-associated molecular patterns (PAMPS), which leads to NF-κB activation. [2]

Fcγ receptors

Fcγ receptors recognise IgG coated targets. The main recognised part is the Fc fragment. 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. [5] Fcγ receptor mediated phagocytosis includes formation of protrusions of the cell called a 'phagocytic cup' and activates an oxidative burst in neutrophils. [4]

Complement receptors

These receptors recognise targets coated in C3b, 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. [5]

Mannose receptors

Mannose 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. [5]

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 lysosomes, forming a phagolysosome and leading to degradation. Progressively, the phagolysosome is acidified, activating degradative enzymes. [2] [7]

Degradation can be oxygen-dependent or oxygen-independent.

Leukocytes generate hydrogen cyanide during phagocytosis, and can kill bacteria, fungi, and other pathogens by generating several other toxic chemicals. [9] [10] [11]

Some bacteria, for example Treponema pallidum , Escheria coli and Staphylococcus aureus , are able to avoid phagocytosis by several mechanisms.

In apoptosis

Following apoptosis, the dying cells need to be taken up into the surrounding tissues by macrophages in a process called efferocytosis. 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. [12] 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, 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. [13] [14] [15] [16]

Trophozoites of Entamoeba histolytica with ingested erythrocytes Trophozoites of Entamoeba histolytica with ingested erythrocytes.JPG
Trophozoites of Entamoeba histolytica with ingested erythrocytes

In protists

In many protists, 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.[ citation needed ]

As in phagocytic immune cells, the resulting phagosome may be merged with lysosomes(food vacuoles) containing digestive enzymes, 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. [18]

Mixotrophy can involve phagotrophic nutrition and phototrophic nutrition. [19]

See also

Related Research Articles

Macrophage Type of white blood cell

Macrophages are a type of white blood cell of the immune system that engulfs and digests anything that does not have, on its surface, proteins that are specific to healthy body cells, including cancer cells, microbes, cellular debris, foreign substances, etc. The process is called phagocytosis, which acts to defend the host against infection and injury.

Phagocyte Cells that ingest harmful matter within the body

Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek phagein, "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek kutos, "hollow vessel". They are essential for fighting infections and for subsequent immunity. Phagocytes are important throughout the animal kingdom and are highly developed within vertebrates. One litre of human blood contains about six billion phagocytes. They were discovered in 1882 by Ilya Ilyich Mechnikov while he was studying starfish larvae. Mechnikov was awarded the 1908 Nobel Prize in Physiology or Medicine for his discovery. Phagocytes occur in many species; some amoebae behave like macrophage phagocytes, which suggests that phagocytes appeared early in the evolution of life.

Kupffer cell

Kupffer cells, also known as stellate macrophages and Kupffer–Browicz cells, are specialized cells localized in liver within the lumen of the liver sinusoids and are adhesive to their endothelial cells which make up the blood vessel walls. Kupffer cells contain the largest amount of tissue-resident macrophages in the body. Gut bacteria, bacterial endotoxins, and microbial debris transported to the liver from the gastrointestinal tract via the portal vein will first come in contact with Kupffer cells, the first immune cells in the liver. It is because of this that any change to Kupffer cell functions can be connected to various liver diseases such as alcoholic liver disease, viral hepatitis, intrahepatic cholestasis, steatohepatitis, activation or rejection of the liver during liver transplantation and liver fibrosis. They form part of the mononuclear phagocyte system.

Opsonins are extracellular proteins that, when bound to substances or cells, induce phagocytes to phagocytose the substances or cells with the opsonins bound. Thus, opsonins act as tags to label things in the body that should be phagocytosed by phagocytes. Different types of things ("targets") can be tagged by opsonins for phagocytosis, including: pathogens, cancer cells, aged cells, dead or dying cells, excess synapses, or protein aggregates. Opsonins helps clear pathogens, as well as dead, dying and diseased cells.

Respiratory burst is the rapid release of the reactive oxygen species (ROS), superoxide anion and hydrogen peroxide, from different cell types.

Phagosome

In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs). A phagosome is formed by the fusion of the cell membrane around a microorganism, a senescent cell or an apoptotic cell. Phagosomes have membrane-bound proteins to recruit and fuse with lysosomes to form mature phagolysosomes. The lysosomes contain hydrolytic enzymes and reactive oxygen species (ROS) which kill and digest the pathogens. Phagosomes can also form in non-professional phagocytes, but they can only engulf a smaller range of particles, and do not contain ROS. The useful materials from the digested particles are moved into the cytosol, and waste is removed by exocytosis. Phagosome formation is crucial for tissue homeostasis and both innate and adaptive host defense against pathogens.

Antibody opsonization The process in which a microorganism (or other particulate material) is rendered more susceptible to phagocytosis by coating with an opsonin, a blood serum protein such as a complement component or antibody.

Antibody opsonization is a process by which a pathogen is marked for destruction by antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), or complement-dependent cytotoxicity (CDC).

Innate immune system One of the two main immunity strategies found in vertebrates

The innate immune system is one of the two main immunity strategies found in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the dominant immune system response found in plants, fungi, insects, and primitive multicellular organisms.

Fc receptor Protein

A Fc receptor is a protein found on the surface of certain cells – including, among others, B lymphocytes, follicular dendritic cells, natural killer cells, macrophages, neutrophils, eosinophils, basophils, human platelets, and mast cells – that contribute to the protective functions of the immune system. Its name is derived from its binding specificity for a part of an antibody known as the Fc region. Fc receptors bind to antibodies that are attached to infected cells or invading pathogens. Their activity stimulates phagocytic or cytotoxic cells to destroy microbes, or infected cells by antibody-mediated phagocytosis or antibody-dependent cell-mediated cytotoxicity. Some viruses such as flaviviruses use Fc receptors to help them infect cells, by a mechanism known as antibody-dependent enhancement of infection.

Immune complex

An immune complex, sometimes called an antigen-antibody complex or antigen-bound antibody, is a molecule formed from the binding of multiple antigens to antibodies. The bound antigen and antibody act as a unitary object, effectively an antigen of its own with a specific epitope. After an antigen-antibody reaction, the immune complexes can be subject to any of a number of responses, including complement deposition, opsonization, phagocytosis, or processing by proteases. Red blood cells carrying CR1-receptors on their surface may bind C3b-coated immune complexes and transport them to phagocytes, mostly in liver and spleen, and return to the general circulation.

Phagolysosome

In biology, a phagolysosome, or endolysosome, is a cytoplasmic body formed by the fusion of a phagosome with a lysosome in a process that occurs during phagocytosis. Formation of phagolysosomes is essential for the intracellular destruction of microorganisms and pathogens. It takes place when the phagosome's and lysosome's membranes 'collide', at which point the lysosomal contents—including hydrolytic enzymes—are discharged into the phagosome in an explosive manner and digest the particles that the phagosome had ingested. Some products of the digestion are useful materials and are moved into the cytoplasm; others are exported by exocytosis.

Alveolar macrophage

An alveolar macrophage, pulmonary macrophage, is a type of macrophage, a professional phagocyte, found in the airways and at the level of the alveoli in the lungs, but separated from their walls.

Collectins (collagen-containing C-type lectins) are a part of the innate immune system. They form a family of collagenous Ca2+-dependent defense lectins, which are found in animals. Collectins are soluble pattern recognition receptors (PRRs). Their function is to bind to oligosaccharide structure or lipids that are on the surface of microorganisms. Like other PRRs they bind pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) of oligosaccharide origin. Binding of collectins to microorganisms may trigger elimination of microorganisms by aggregation, complement activation, opsonization, activation of phagocytosis, or inhibition of microbial growth. Other functions of collectins are modulation of inflammatory, allergic responses, adaptive immune system and clearance of apoptotic cells.

A complement receptor is a membrane-bound receptor belonging to the complement system, which is part of the innate immune system. Complement receptors bind effector protein fragments that are produced in response to antigen-antibody complexes or damage-associated molecules. Complement receptor activation contributes to the regulation of inflammation, leukocyte extravasation, and phagocytosis; it also contributes to the adaptive immune response. Different complement receptors can participate in either the classical complement pathway, the alternative complement pathway, or both.

The mannose receptor is a C-type lectin primarily present on the surface of macrophages, immature dendritic cells and liver sinusoidal endothelial cells, but is also expressed on the surface of skin cells such as human dermal fibroblasts and keratinocytes. It is the first member of a family of endocytic receptors that includes Endo180 (CD280), M-type PLA2R, and DEC-205 (CD205).

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 apoptotic cells for phagocytosis. Additionally, C3b plays a role in forming a C3 convertase when bound to Factor B, or a C5 convertase when bound to C4b and C2b or when an additional C3b molecule binds to the C3bBb complex.

CD16, also known as FcγRIII, is a cluster of differentiation molecule found on the surface of natural killer cells, neutrophils, monocytes, and macrophages. CD16 has been identified as Fc receptors FcγRIIIa (CD16a) and FcγRIIIb (CD16b), which participate in signal transduction. The most well-researched membrane receptor implicated in triggering lysis by NK cells, CD16 is a molecule of the immunoglobulin superfamily (IgSF) involved in antibody-dependent cellular cytotoxicity (ADCC). It can be used to isolate populations of specific immune cells through fluorescent-activated cell sorting (FACS) or magnetic-activated cell sorting, using antibodies directed towards CD16.

A non-specific immune cell is an immune cell that responds to many antigens, not just one antigen. Non-specific immune cells function in the first line of defense against infection or injury. The innate immune system is always present at the site of infection and ready to fight the bacteria; it can also be referred to as the "natural" immune system. The cells of the innate immune system do not have specific responses and respond to each foreign invader using the same mechanism.

Apoptotic-cell associated molecular patterns (ACAMPs) are molecular markers present on cells which are going through apoptosis, i.e. programmed cell death. The term was used for the first time by C. D. Gregory in 2000. Recognition of these patterns by the pattern recognition receptors (PRRs) of phagocytes then leads to phagocytosis of the apoptotic cell. These patterns include eat-me signals on the apoptotic cells, loss of don’t-eat-me signals on viable cells and come-get-me signals ) secreted by the apoptotic cells in order to attract phagocytes. Thanks to these markers, apoptotic cells, unlike necrotic cells, do not trigger the unwanted immune response.

Phagoptosis is a type of cell death caused by the cell being phagocytosed by another cell, and therefore this form of cell death is prevented by blocking phagocytosis.

References

  1. Ambrose, Charles T. (2006). "The Osler slide, a demonstration of phagocytosis from 1876: Reports of phagocytosis before Metchnikoff's 1880 paper". Cellular Immunology. 240 (1): 1–4. doi:10.1016/j.cellimm.2006.05.008. PMID   16876776.
  2. 1 2 3 4 Gordon, Siamon (March 2016). "Phagocytosis: An Immunobiologic Process". Immunity. 44 (3): 463–475. doi: 10.1016/j.immuni.2016.02.026 . PMID   26982354.
  3. 1 2 3 4 5 6 M.), Murphy, Kenneth (Kenneth (2012). Janeway's immunobiology. Travers, Paul, 1956-, Walport, Mark., Janeway, Charles. (8th ed.). New York: Garland Science. ISBN   9780815342434. OCLC   733935898.
  4. 1 2 3 Witko-Sarsat, Véronique; Rieu, Philippe; Descamps-Latscha, Béatrice; Lesavre, Philippe; Halbwachs-Mecarelli, Lise (May 2000). "Neutrophils: Molecules, Functions and Pathophysiological Aspects". Laboratory Investigation. 80 (5): 617–653. doi: 10.1038/labinvest.3780067 . ISSN   0023-6837. PMID   10830774.
  5. 1 2 3 4 5 Aderem, Alan; Underhill, David M. (April 1999). "Mechanisms of Phagocytosis in Macrophages". Annual Review of Immunology. 17 (1): 593–623. doi:10.1146/annurev.immunol.17.1.593. ISSN   0732-0582. PMID   10358769.
  6. The Immune System, Peter Parham, Garland Science, 2nd edition
  7. Flannagan, Ronald S.; Jaumouillé, Valentin; Grinstein, Sergio (2012-02-28). "The Cell Biology of Phagocytosis". Annual Review of Pathology: Mechanisms of Disease. 7 (1): 61–98. doi:10.1146/annurev-pathol-011811-132445. ISSN   1553-4006. PMID   21910624.
  8. Hemilä, Harri (1992). "Vitamin C and the common cold". British Journal of Nutrition. 67 (1): 3–16. doi: 10.1079/bjn19920004 . PMID   1547201.
  9. Borowitz JL, Gunasekar PG, Isom GE (12 Sep 1997). "Hydrogen cyanide generation by mu-opiate receptor activation: possible neuromodulatory role of endogenous cyanide". Brain Research . 768 (1–2): 294–300. doi:10.1016/S0006-8993(97)00659-8. PMID   9369328. S2CID   12277593.
  10. Stelmaszyńska, T (1985). "Formation of HCN by human phagocytosing neutrophils--1. Chlorination of Staphylococcus epidermidis as a source of HCN". Int J Biochem. 17 (3): 373–9. doi:10.1016/0020-711x(85)90213-7. PMID   2989021.
  11. Zgliczyński, Jan Maciej; Stelmaszyńska, Teresa (1988). The Respiratory Burst and its Physiological Significance. pp. 315–347. doi:10.1007/978-1-4684-5496-3_15. ISBN   978-1-4684-5498-7.
  12. Bilyy RO, Shkandina T, Tomin A, Muñoz LE, Franz S, Antonyuk V, Kit YY, Zirngibl M, Fürnrohr BG, Janko C, Lauber K, Schiller M, Schett G, Stoika RS, Herrmann M (January 2012). "Macrophages discriminate glycosylation patterns of apoptotic cell-derived microparticles". The Journal of Biological Chemistry. 287 (1): 496–503. doi: 10.1074/jbc.M111.273144 . PMC   3249103 . PMID   22074924.
  13. Mukundan L, Odegaard JI, Morel CR, Heredia JE, Mwangi JW, Ricardo-Gonzalez RR, Goh YP, Eagle AR, Dunn SE, Awakuni JU, Nguyen KD, Steinman L, Michie SA, Chawla A (November 2009). "PPAR-delta senses and orchestrates clearance of apoptotic cells to promote tolerance". Nature Medicine. 15 (11): 1266–72. doi:10.1038/nm.2048. PMC   2783696 . PMID   19838202.
  14. Roszer, T; Menéndez-Gutiérrez, MP; Lefterova, MI; Alameda, D; Núñez, V; Lazar, MA; Fischer, T; Ricote, M (Jan 1, 2011). "Autoimmune kidney disease and impaired engulfment of apoptotic cells in mice with macrophage peroxisome proliferator-activated receptor gamma or retinoid X receptor alpha deficiency". Journal of Immunology. 186 (1): 621–31. doi:10.4049/jimmunol.1002230. PMC   4038038 . PMID   21135166.
  15. Kruse, K; Janko, C; Urbonaviciute, V; Mierke, CT; Winkler, TH; Voll, RE; Schett, G; Muñoz, LE; Herrmann, M (September 2010). "Inefficient clearance of dying cells in patients with SLE: anti-dsDNA autoantibodies, MFG-E8, HMGB-1 and other players". Apoptosis. 15 (9): 1098–113. doi:10.1007/s10495-010-0478-8. PMID   20198437. S2CID   12729066.
  16. Han, CZ; Ravichandran, KS (Dec 23, 2011). "Metabolic connections during apoptotic cell engulfment". Cell. 147 (7): 1442–5. doi:10.1016/j.cell.2011.12.006. PMC   3254670 . PMID   22196723.
  17. Grønlien HK, Berg T, Løvlie AM (July 2002). "In the polymorphic ciliate Tetrahymena vorax, the non-selective phagocytosis seen in microstomes changes to a highly selective process in macrostomes". The Journal of Experimental Biology. 205 (Pt 14): 2089–97. doi:10.1242/jeb.205.14.2089. PMID   12089212.
  18. Montagnes, Djs; Barbosa, Ab; Boenigk, J; Davidson, K; Jürgens, K; Macek, M; Parry, Jd; Roberts, Ec; imek, K (2008-09-18). "Selective feeding behaviour of key free-living protists: avenues for continued study". Aquatic Microbial Ecology. 53: 83–98. doi: 10.3354/ame01229 . ISSN   0948-3055.
  19. Stibor H, Sommer U (April 2003). "Mixotrophy of a photosynthetic flagellate viewed from an optimal foraging perspective". Protist. 154 (1): 91–8. doi:10.1078/143446103764928512. PMID   12812372.