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 granulocytes (neutrophils, basophils, and eosinophils) and mast cells. It is also used by certain lymphocytes such as natural killer (NK) cells and cytotoxic T cells, whose main purpose is to destroy invading microorganisms.

The degranulation process in a Mast cell. 1 = antigen; 2 = IgE; 3 = FcεR1; 4 = preformed mediators (histamine, proteases, chemokines, heparin); 5 = granules; 6 - Mast cell; 7 - newly formed mediators (prostaglandins, leukotrienes, thromboxanes, platelet-activating factor)

Mast cells

Degranulation in mast cells is part of an inflammatory response, and substances such as histamine are released. Granules from mast cells mediate processes such as "vasodilation, vascular homeostasis, innate and adaptive immune responses, angiogenesis, and venom detoxification."[1]

Antigens interact with IgE molecules already bound to high affinity Fc receptors on the surface of mast cells to induce degranulation, via the activation of tyrosine kinases within the cell. The mast cell releases a mixture of compounds, including histamine, proteoglycans, serotonin, and serine proteases from its cytoplasmic granules.[2]

Eosinophils

In a similar mechanism, activated eosinophils release preformed mediators such as major basic protein, and enzymes such as peroxidase, following interaction between their Fc receptors and IgE molecules that are bound to large parasites like helminths.[3][4]

Neutrophils

Degranulation in neutrophils can occur in response to infection, and the resulting granules are released in order to protect against tissue damage. Excessive degranulation of neutrophils, sometimes triggered by bacteria, is associated with certain inflammatory disorders, such as asthma and septic shock.[5][6]

Four kinds of granules exist in neutrophils that display differences in content and regulation. Secretory vesicles are the most likely to release their contents by degranulation, followed by gelatinase granules, specific granules, and azurophil granules.[7] [8]

Cytotoxic T cells and NK cells

Cytotoxic T cells and NK cells release molecules like perforin and granzymes by a process of directed exocytosis to kill infected target cells.[9]

See also

References
  1. Krystel-Whittemore, Melissa; Dileepan, Kottarappat N.; Wood, John G. (2016). "Mast Cell: A Multi-Functional Master Cell". Frontiers in Immunology. 6. doi:10.3389/fimmu.2015.00620. ISSN 1664-3224. PMID 26779180.
  2. Yamasaki S, Saito T (2005). "Regulation of mast cell activation through FcepsilonRI". Chem Immunol Allergy. Chemical Immunology and Allergy. 87: 22–31. doi:10.1159/000087568. ISBN 3-8055-7948-9. PMID 16107760.
  3. David J, Butterworth A, Vadas M (1980). "Mechanism of the interaction mediating killing of Schistosoma mansoni by human eosinophils". Am J Trop Med Hyg. 29 (5): 842–8. doi:10.4269/ajtmh.1980.29.842. PMID 7435788.
  4. Capron M, Soussi Gounni A, Morita M, Truong M, Prin L, Kinet J, Capron A (1995). "Eosinophils: from low- to high-affinity immunoglobulin E receptors". Allergy. 50 (25 Suppl): 20–23. doi:10.1111/j.1398-9995.1995.tb04270.x. PMID 7677229. S2CID 36197719.
  5. Gierlikowska, Barbara; Stachura, Albert; Gierlikowski, Wojciech; Demkow, Urszula (2021). "Phagocytosis, Degranulation and Extracellular Traps Release by Neutrophils—The Current Knowledge, Pharmacological Modulation and Future Prospects". Frontiers in Pharmacology. 12. doi:10.3389/fphar.2021.666732. ISSN 1663-9812. PMID 34017259.
  6. Lacy, Paige (2006-09-15). "Mechanisms of Degranulation in Neutrophils". Allergy, Asthma & Clinical Immunology. 2 (3): 98. doi:10.1186/1710-1492-2-3-98. ISSN 1710-1492. PMC 2876182. PMID 20525154.
  7. Faurschou M, Borregaard N (2003). "Neutrophil granules and secretory vesicles in inflammation". Microbes Infect. 5 (14): 1317–1327. doi:10.1016/j.micinf.2003.09.008. PMID 14613775.
  8. Lominadze G, Powell D, Luerman G, Link A, Ward R, McLeish K (2005). "Proteomic analysis of human neutrophil granules" (PDF). Mol Cell Proteomics. 4 (10): 1503–1521. doi:10.1074/mcp.M500143-MCP200. PMID 15985654.
  9. Veugelers K, Motyka B, Frantz C, Shostak I, Sawchuk T, Bleackley R (2004). "The granzyme B-serglycin complex from cytotoxic granules requires dynamin for endocytosis". Blood. 103 (10): 3845–3853. doi:10.1182/blood-2003-06-2156. PMID 14739229. S2CID 23814556.
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