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Phagocytosis
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<h2 id="history">History</h2> <p>The history of phagocytosis represents the scientific establishment of immunology as the process is the first immune response mechanism discovered and understood as such.<a class="footnote-ref" id="fnref:1" href="#fn:1"><sup>1</sup></a><a class="footnote-ref" id="fnref:2" href="#fn:2"><sup>2</sup></a> The earliest definitive account of cell eating was given by Swiss scientist <a href="/facts/Albert_von_K%C3%B6lliker/eYudoEHx">Albert von Kölliker</a> in 1849.<a class="footnote-ref" id="fnref:3" href="#fn:3"><sup>3</sup></a> In his report in <i>Zeitschrift für Wissenschaftliche Zoologie,</i> Kölliker described the feeding process of an amoeba-like alga, <i><a href="/facts/Actinophryid/UIQdVgGY">Actinophyrys sol</a></i> (a <a href="/facts/Heliozoan/8deksNRy">heliozoan</a>) mentioning details of how the protist engulfed and swallowed (the process now called endocytosis) a small organism, that he named <a href="/facts/Infusoria/oLTsxd6c">infusoria</a> (a generic name for microbes at the time).<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> </p><p>The first demonstration of phagocytosis as a property of leucocytes, the immune cells, was from the German zoologist <a href="/facts/Ernst_Haeckel/osqrW7hB">Ernst Haeckel</a>.<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a><a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> Haeckel discovered that blood cells of sea slug, <i><a href="/facts/Tethys_fimbria/SqbKCPBV">Tethys</a></i>, could ingest <a href="/facts/Indian_ink/2XDG4WMh">Indian ink</a> (or <a href="/facts/Indigo/ICSGEsqH">indigo</a><a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a>) particles. It was the first direct evidence of phagocytosis by immune cells.<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a><a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> Haeckel reported his experiment in a 1862 monograph <i>Die Radiolarien (Rhizopoda Radiaria): Eine Monographie.</i><a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> </p><p>Phagocytosis was noted by Canadian physician <a href="/facts/William_Osler/xRwrwyzc">William Osler</a> (1876),<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> and later studied and named by <a href="/facts/%C3%89lie_Metchnikoff/GeLMnBvl">Élie Metchnikoff</a> (1880, 1883).<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a> </p> <h2 id="in-immune-system">In immune system</h2> <p class="note">Main article: <a href="/facts/Phagocyte/1vbsR9er">Phagocyte</a></p> <p>Phagocytosis is one main mechanisms of the <a href="/facts/Innate_immune_system/lz4BpSQI">innate immune</a> defense. It is one of the first processes responding to <a href="/facts/Infection/182XrncP">infection</a>, and is also one of the initiating branches of an <a href="/facts/Adaptive_immune_system/bc7zT1Jo">adaptive immune</a> 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 <a href="/facts/Invertebrate/3CyqCVnN">invertebrates</a>.<a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a> </p> <h3>Professional phagocytic cells</h3> <p><a href="/facts/Neutrophil/KL6oTt8b">Neutrophils</a>, <a href="/facts/Macrophage/z7hkQu3o">macrophages</a>, <a href="/facts/Monocyte/FW4NNMKM">monocytes</a>, <a href="/facts/Dendritic_cell/19KBuKFK">dendritic cells</a>, <a href="/facts/Osteoclast/jHHtEQru">osteoclasts</a> and <a href="/facts/Eosinophil/yhIKA8bE">eosinophils</a> can be classified as professional phagocytes.<a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a> The first three have the greatest role in immune response to most infections.<a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a> </p><p>The role of neutrophils is patrolling the bloodstream and rapid migration to the tissues in large numbers only in case of infection.<a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a> 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 <a href="/facts/Collagenase/IWkePfvJ">collagenase</a>, <a href="/facts/Gelatinase/JzPx4AQW">gelatinase</a> or <a href="/facts/Serine_protease/kGfEE6hE">serine proteases</a>, <a href="/facts/Myeloperoxidase/UqYpgUrh">myeloperoxidase</a>, <a href="/facts/Lactoferrin/UpV8FC7f">lactoferrin</a> and antibiotic proteins. Degranulation of these into the phagosome, accompanied by high <a href="/facts/Reactive_oxygen_species/GpwSRugH">reactive oxygen species</a> production <a href="/facts/Respiratory_burst/QW5htP4n">(oxidative burst)</a> is highly microbicidal.<a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a> </p><p>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.<a class="footnote-ref" id="fnref:18" href="#fn:18"><sup>18</sup></a> Macrophages initiate phagocytosis by <a href="/facts/Mannose_receptor/x2JClStd">mannose receptors</a>, <a href="/facts/Scavenger_receptor_(immunology)/EXnj4Lvp">scavenger receptors</a>, <a href="/facts/Fc_receptor/hpv5q6Hu">Fcγ receptors</a> and <a href="/facts/Complement_receptor/EsI570Ic">complement receptors</a> 1, 3 and 4. Macrophages are long-lived and can continue phagocytosis by forming new lysosomes.<a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a><a class="footnote-ref" id="fnref:20" href="#fn:20"><sup>20</sup></a> </p><p>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 <a href="/facts/Antigen_presentation/RMEAcYwR">antigen presentation</a> to the cells of the adaptive immune system.<a class="footnote-ref" id="fnref:21" href="#fn:21"><sup>21</sup></a> </p> <h3>Initiating receptors</h3> <p>Receptors for phagocytosis can be divided into two categories by recognised molecules. The first, opsonic receptors, are dependent on <a href="/facts/Opsonin/wKPBjS1t">opsonins</a>.<a class="footnote-ref" id="fnref:22" href="#fn:22"><sup>22</sup></a> Among these are receptors that recognise the Fc part of bound <a href="/facts/Immunoglobulin_G/cKzc83tk">IgG</a> antibodies, deposited <a href="/facts/Complement_system/vRSrQDUv">complement</a> or receptors, that recognise other opsonins of cell or plasma origin. Non-opsonic receptors include lectin-type receptors, <a href="/facts/Dectin_1/hPPxd0e6">Dectin</a> receptor, or scavenger receptors. Some phagocytic pathways require a second signal from <a href="/facts/Pattern_recognition_receptor/ItopNrK0">pattern recognition receptors</a> (PRRs) activated by attachment to <a href="/facts/Pathogen-associated_molecular_pattern/jLrjQv7T">pathogen-associated molecular patterns</a> (PAMPS), which leads to <a href="/facts/NF-%CE%BAB/qcpt5vuQ">NF-κB</a> activation.<a class="footnote-ref" id="fnref:23" href="#fn:23"><sup>23</sup></a> </p> <h4>Fcγ receptors</h4> <p>Fcγ receptors recognise IgG coated targets. The main recognised part is the <a href="/facts/Fragment_crystallizable_region/hC7E3AMe">Fc fragment</a>. The molecule of the receptor contain an intracellular <a href="/facts/Immunoreceptor_tyrosine-based_activation_motif/YQe88zIs">ITAM domain</a> 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 <a href="/facts/Fc%CE%B3RI/LAFFWxoE">FcγRI</a>, <a href="/facts/Fc%CE%B3RIIA/VFW8eISr">FcγRIIA</a>, and <a href="/facts/Fc%CE%B3RIIIA/ybJdeTej">FcγRIII</a>.<a class="footnote-ref" id="fnref:24" href="#fn:24"><sup>24</sup></a> Fcγ receptor mediated phagocytosis includes formation of protrusions of the cell called a 'phagocytic cup' and activates an oxidative burst in neutrophils.<a class="footnote-ref" id="fnref:25" href="#fn:25"><sup>25</sup></a> </p> <h4>Complement receptors</h4> <p>These receptors recognise targets coated in <a href="/facts/C3b/gQ2bfe0R">C3b</a>, <a href="/facts/Complement_component_4/nqX5xhav">C4b</a> 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 <a href="/facts/Complement_receptor_1/ShQaxyLT">CR1</a>, <a href="/facts/Complement_Receptor_3/ft7kK5a7">CR3</a> and CR4 are responsible for recognition of targets. Complement coated targets are internalised by 'sinking' into the phagocyte membrane, without any protrusions.<a class="footnote-ref" id="fnref:26" href="#fn:26"><sup>26</sup></a> </p> <h4>Mannose receptors</h4> <p><a href="/facts/Mannose/U05bJ7p8">Mannose</a> and other pathogen-associated sugars, such as <a href="/facts/Fucose/WeW1TEx5">fucose</a>, 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.<a class="footnote-ref" id="fnref:27" href="#fn:27"><sup>27</sup></a> </p> <h3>Phagosome</h3> <p>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 <a href="/facts/Centrosome/QlTtIIeI">centrosome</a> of the phagocyte and is fused with <a href="/facts/Lysosome/0mcrzJU9">lysosomes</a>, forming a <a href="/facts/Phagolysosome/gtbTG32S">phagolysosome</a> and leading to degradation. Progressively, the phagolysosome is acidified, activating degradative enzymes.<a class="footnote-ref" id="fnref:28" href="#fn:28"><sup>28</sup></a><a class="footnote-ref" id="fnref:29" href="#fn:29"><sup>29</sup></a> </p><p>Degradation can be oxygen-dependent or oxygen-independent. </p> <ul><li>Oxygen-dependent degradation depends on <a href="/facts/NADPH/XMgmPQ5t">NADPH</a> and the production of <a href="/facts/Reactive_oxygen_species/GpwSRugH">reactive oxygen species</a>. <a href="/facts/Hydrogen_peroxide/vju6HBIc">Hydrogen peroxide</a> and <a href="/facts/Myeloperoxidase/UqYpgUrh">myeloperoxidase</a> activate a halogenating system, which leads to the creation of <a href="/facts/Hypochlorite/XMJdjAEM">hypochlorite</a> and the destruction of bacteria.<a class="footnote-ref" id="fnref:30" href="#fn:30"><sup>30</sup></a></li> <li>Oxygen-independent degradation depends on the release of granules, containing enzymes such as <a href="/facts/Lysozyme/VQqTSbFS">lysozymes</a>, <a href="/facts/Bactericidal_permeability-increasing_protein/2QMqvn1s">Bactericidal permeability-increasing protein</a>, <a href="/facts/Major_basic_protein/VD2SMdvE">Major basic protein</a> and cationic proteins such as <a href="/facts/Defensin/BjSyPRDT">defensins</a>. Other antimicrobial peptides are present in these granules, including <a href="/facts/Lactoferrin/UpV8FC7f">lactoferrin</a>, which sequesters <a href="/facts/Iron/QK1JYy8E">iron</a> 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.<a class="footnote-ref" id="fnref:31" href="#fn:31"><sup>31</sup></a><a class="footnote-ref" id="fnref:32" href="#fn:32"><sup>32</sup></a></li></ul> <p><a href="/facts/Leukocyte/vsDunUK0">Leukocytes</a> generate <a href="/facts/Hydrogen_cyanide/vNtA0Mxe">hydrogen cyanide</a> during phagocytosis, and can kill <a href="/facts/Bacteria/wC8xSCsU">bacteria</a>, <a href="/facts/Fungi/BHo5DP59">fungi</a>, and other pathogens by generating several other toxic chemicals.<a class="footnote-ref" id="fnref:33" href="#fn:33"><sup>33</sup></a><a class="footnote-ref" id="fnref:34" href="#fn:34"><sup>34</sup></a><a class="footnote-ref" id="fnref:35" href="#fn:35"><sup>35</sup></a> </p><p>Some bacteria, for example <i><a href="/facts/Treponema_pallidum/33nBmQTg">Treponema pallidum</a></i>, <i><a href="/facts/Escheria_coli/nR4Gvl56">Escheria coli</a></i> and <i><a href="/facts/Staphylococcus_aureus/9yDVBMsc">Staphylococcus aureus</a></i>, are able to avoid phagocytosis by several mechanisms. </p> <h2 id="in-apoptosis">In apoptosis</h2><p> Following <a href="/facts/Apoptosis/8dVzSm4y">apoptosis</a>, the dying cells need to be taken up into the surrounding tissues by macrophages in a process called <a href="/facts/Efferocytosis/XANRMk2D">efferocytosis</a>. One of the features of an apoptotic cell is the presentation of a variety of intracellular molecules on the cell surface, such as <a href="/facts/Calreticulin/gBGh7vLu">calreticulin</a>, <a href="/facts/Phosphatidylserine/LLq1N91L">phosphatidylserine</a> (from the inner layer of the plasma membrane), <a href="/facts/Annexin_A1/Y8r4zp9c">annexin A1</a>, oxidised <a href="/facts/LDL/R5VLPxAg">LDL</a> and altered <a href="/facts/Glycans/FbMG78sx">glycans</a>.<a class="footnote-ref" id="fnref:36" href="#fn:36"><sup>36</sup></a> 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 <a href="/facts/Thrombospondin_1/um2Hk2RQ">thrombospondin 1</a>, <a href="/facts/GAS6/ng4BakeI">GAS6</a>, and <a href="/facts/MFGE8/br9FdAhv">MFGE8</a>, which themselves then bind to other receptors on the macrophage such as <a href="/facts/CD36/68dNYlC2">CD36</a> and <a href="/facts/Alpha-v_beta-3/a28UtVdI">alpha-v beta-3 integrin</a>. 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.<a class="footnote-ref" id="fnref:37" href="#fn:37"><sup>37</sup></a><a class="footnote-ref" id="fnref:38" href="#fn:38"><sup>38</sup></a><a class="footnote-ref" id="fnref:39" href="#fn:39"><sup>39</sup></a><a class="footnote-ref" id="fnref:40" href="#fn:40"><sup>40</sup></a></p> <h2 id="in-protists">In protists</h2> <p>Phagocytosis is used by many <a href="/facts/Protists/NYVfaGVz">protists</a> as a means of feeding, thus constituting phagotrophy. </p> <ul><li>In some, such as <a href="/facts/Amoeba/xxvUal7B">amoeba</a>, phagocytosis takes place by surrounding the target object with <a href="/facts/Pseudopod/EHHnuk4f">pseudopods</a>, as in animal phagocytes. In humans, the amoebozoan <i><a href="/facts/Entamoeba_histolytica/lMPf2xDp">Entamoeba histolytica</a></i> can phagocytose <a href="/facts/Red_blood_cell/Kggpq8Jh">red blood cells</a>.</li> <li><a href="/facts/Ciliate/UREaeHEc">Ciliates</a> also engage in phagocytosis.<a class="footnote-ref" id="fnref:41" href="#fn:41"><sup>41</sup></a> In ciliates there is a specialized groove or chamber in the cell where phagocytosis takes place, called the <a href="/facts/Cytostome/KBseD42I">cytostome</a> or mouth.</li></ul> <p>As in phagocytic immune cells, the resulting phagosome may be merged with lysosomes (<a href="/facts/Food_vacuole/DJW5xHSt">food vacuoles</a>) containing digestive <a href="/facts/Enzyme/DSI1Fh7y">enzymes</a>, forming a <a href="/facts/Phagolysosome/gtbTG32S">phagolysosome</a>. The food particles will then be digested, and the released nutrients are diffused or transported into the <a href="/facts/Cytosol/VyXgygWm">cytosol</a> for use in other metabolic processes.<a class="footnote-ref" id="fnref:42" href="#fn:42"><sup>42</sup></a> </p><p><a href="/facts/Mixotrophy/S7ePtbLm">Mixotrophy</a> can involve phagotrophic nutrition and <a href="/facts/Phototroph/g8gH5q72">phototrophic</a> nutrition.<a class="footnote-ref" id="fnref:43" href="#fn:43"><sup>43</sup></a> </p> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/Active_transport/7EAcsfb2">Active transport</a></li> <li><a href="/facts/Antigen_presentation/RMEAcYwR">Antigen presentation</a></li> <li><a href="/facts/Antigen-presenting_cell/No0wr2uU">Antigen-presenting cell</a></li> <li><a href="/facts/Emperipolesis/3vjBuhC7">Emperipolesis</a></li> <li><a href="/facts/Endosymbiont/eWvSS8ID">Endosymbionts in protists</a></li> <li><a href="/facts/Paracytophagy/lweRtBPK">Paracytophagy</a></li> <li><a href="/facts/Phagoptosis/LsFDBSdz">Phagoptosis</a></li> <li><a href="/facts/Pinocytosis/99D49uSV">Pinocytosis</a></li> <li><a href="/facts/Residual_body/HEKfQE5P">Residual body</a></li> <li><a href="/facts/Cell_wall/DYXJVrnw">Cell wall</a></li></ul> <h2 id="external-links">External links</h2> <a href="/facts/Wikisource/TrMdylNf">Wikisource</a> has the text of the <a href="/facts/Encyclop%C3%A6dia_Britannica_Eleventh_Edition/mPElbCRY">1911 <i>Encyclopædia Britannica</i></a> article "Phagocytosis". <ul><li> Media related to Phagocytosis at Wikimedia Commons</li> <li><a href="https://meshb.nlm.nih.gov/record/ui?name=Phagocytosis">Phagocytosis</a> at the U.S. National Library of Medicine <a href="/facts/Medical_Subject_Headings/C57g2JuF">Medical Subject Headings</a> (MeSH)</li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Tauber, A. I. (1992). "The birth of immunology. III. The fate of the phagocytosis theory". Cellular Immunology. 139 (2): 505–530. doi:10.1016/0008-8749(92)90089-8. ISSN 0008-8749. PMID 1733516. <a href="https://doi.org/10.1016%2F0008-8749%2892%2990089-8" target="_blank">https://doi.org/10.1016%2F0008-8749%2892%2990089-8</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Teti, Giuseppe; Biondo, Carmelo; Beninati, Concetta (2016). "The Phagocyte, Metchnikoff, and the Foundation of Immunology". Microbiology Spectrum. 4 (2): MCHD-0009-2015 (online). doi:10.1128/microbiolspec.MCHD-0009-2015. ISSN 2165-0497. PMID 27227301. <a href="https://doi.org/10.1128%2Fmicrobiolspec.MCHD-0009-2015" target="_blank">https://doi.org/10.1128%2Fmicrobiolspec.MCHD-0009-2015</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Stossel, Thomas P. (1999), "The early history of phagocytosis", Phagocytosis: The Host, Advances in Cellular and Molecular Biology of Membranes and Organelles, vol. 5, Elsevier, pp. 3–18, doi:10.1016/s1874-5172(99)80025-x, ISBN 978-1-55938-999-0, retrieved 2023-04-06 <a href="978-1-55938-999-0" target="_blank">978-1-55938-999-0</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Hallett, Maurice B. (2020). "A Brief History of Phagocytosis". Molecular and Cellular Biology of Phagocytosis. Advances in Experimental Medicine and Biology. Vol. 1246. pp. 9–42. doi:10.1007/978-3-030-40406-2_2. ISBN 978-3-030-40405-5. ISSN 0065-2598. PMID 32399823. S2CID 218618570. <a href="978-3-030-40405-5" target="_blank">978-3-030-40405-5</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Cheng, Thomas C. (1983). "The role of lysosomes in molluscan inflammation". American Zoologist. 23 (1): 129–144. doi:10.1093/icb/23.1.129. ISSN 0003-1569. <a href="https://academic.oup.com/icb/article-lookup/doi/10.1093/icb/23.1.129" target="_blank">https://academic.oup.com/icb/article-lookup/doi/10.1093/icb/23.1.129</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Cheng, Thomas C. (1977), Bulla, Lee A.; Cheng, Thomas C. (eds.), "Biochemical and Ultrastructural Evidence for the Double Role of Phagocytosis in Molluscs: Defense and Nutrition", Comparative Pathobiology, Boston, MA: Springer US, pp. 21–30, doi:10.1007/978-1-4615-7299-2_2, ISBN 978-1-4615-7301-2, retrieved 2023-04-07 <a href="978-1-4615-7301-2" target="_blank">978-1-4615-7301-2</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Rebuck, J. W.; Crowley, J. H. (1955-03-24). "A method of studying leukocytic functions in vivo". Annals of the New York Academy of Sciences. 59 (5): 757–805. doi:10.1111/j.1749-6632.1955.tb45983.x. ISSN 0077-8923. PMID 13259351. 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