{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T11:23:38Z","timestamp":1783077818962,"version":"3.54.6"},"reference-count":115,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Eosinophils are highly granulated white blood and tissue cells that play complex roles in the immune system including host protection against helminthic parasites, viruses, fungi, and bacteria. These bone marrow-derived cells cause tissue damage in a range of diseases and disorders, particularly in allergy, asthma, and chronic rhinosinusitis with nasal polyps. Eosinophils are recruited to tissues in response to chemotactic signals, and during inflammation, they release a plethora of mediators, including immunoregulatory cytokines, through multiple pathways involving degranulation, respiratory burst, lipid mediator release, exosome release, and extracellular trap formation. Degranulation from eosinophils has been implicated as a major effector mechanism in airway diseases, particularly late phase asthma responses and in nasal polyps from patients with chronic rhinosinusitis. In degranulation responses, eosinophils release numerous granule proteins by classical exocytosis, compound exocytosis, piecemeal degranulation, and cytolysis, which refers to cell lysis through membrane rupture and cell destruction. Cytolysis can lead to suicidal extracellular trap formation, which is a regulated form of cell death involving the release of extracellular DNA traps and granule proteins. Granule release from eosinophils is dependent on activation of specific and tightly regulated intracellular signaling pathways, including Rac and Rab guanosine triphosphatases, soluble NSF attachment protein (SNAP) receptors (SNAREs), Cdk5 kinase, and actin dynamics. These observations have shown selective and nonredundant roles for signaling in degranulation responses. In this review, we explore findings from the literature on the mechanisms controlling granule-derived mediator release from eosinophils.<\/jats:p>","DOI":"10.3390\/cells15131211","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T09:34:11Z","timestamp":1783071251000},"page":"1211","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanisms of Eosinophil Degranulation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9638-398X","authenticated-orcid":false,"given":"Sarah","family":"Almas","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery, University of Alberta, Edmonton, AB T6G 2B7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8885-6011","authenticated-orcid":false,"given":"Paige","family":"Lacy","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, 559 Heritage Medical Research Centre, Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1111\/j.1365-2222.2008.02958.x","article-title":"Eosinophils: Biological properties and role in health and disease","volume":"38","author":"Hogan","year":"2008","journal-title":"Clin. Exp. Allergy"},{"key":"ref_2","unstructured":"Means, R.T., Dispenzieri, A., Rodgers, G.M., Fehniger, T.A., Glader, B., Michaelis, L., Arber, D.A., Leonard, J.P., and Appelbaum, F.R. (2024). The Human Eosinophil. Wintrobe\u2019s Clinical Hematology, Wolters Kluwer."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/imm.70104","article-title":"Eosinophil Biology Today-A Primer for Basic and Clinical Investigators","volume":"178","author":"Vieira","year":"2026","journal-title":"Immunology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1016\/j.immuni.2024.04.027","article-title":"Single-cell proteomics and transcriptomics capture eosinophil development and identify the role of IL-5 in their lineage transit amplification","volume":"57","author":"Jorssen","year":"2024","journal-title":"Immunity"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.1600-065X.2011.01026.x","article-title":"Eosinophils: Multifaceted biological properties and roles in health and disease","volume":"242","author":"Kita","year":"2011","journal-title":"Immunol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.pharmthera.2016.10.016","article-title":"Monoclonal antibody therapy for the treatment of asthma and chronic obstructive pulmonary disease with eosinophilic inflammation","volume":"169","author":"Nixon","year":"2017","journal-title":"Pharmacol. Ther."},{"key":"ref_7","unstructured":"Lee, J.J., and Rosenberg, H.F. (2013). Eosinophil-Mediated Responses Toward Helminths. Eosinophils in Health and Disease, Elsevier."},{"key":"ref_8","unstructured":"Lee, J.J., and Rosenberg, H.F. (2013). Antifungal Immunity by Eosinophils: Mechanisms and Implications in Human Diseases. Eosinophils in Health and Disease, Elsevier."},{"key":"ref_9","unstructured":"Lee, J.J., and Rosenberg, H.F. (2013). Immune Responses in Helminth Infections. Eosinophils in Health and Disease, Elsevier."},{"key":"ref_10","unstructured":"Lee, J.J., and Rosenberg, H.F. (2013). Interactions of Eosinophils with Respiratory Virus Pathogens. Eosinophils in Health and Disease, Elsevier."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1093\/cei\/uxac038","article-title":"The regulatory role of eosinophils in viral, bacterial, and fungal infections","volume":"209","author":"Gaur","year":"2022","journal-title":"Clin. Exp. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1111\/j.1365-2222.2010.03484.x","article-title":"Eosinophils in health and disease: The LIAR hypothesis","volume":"40","author":"Lee","year":"2010","journal-title":"Clin. Exp. Allergy"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1111\/all.12169","article-title":"The consequences of not having eosinophils","volume":"68","author":"Gleich","year":"2013","journal-title":"Allergy"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1146\/annurev-immunol-093019-125918","article-title":"Eosinophil Knockout Humans: Uncovering the Role of Eosinophils Through Eosinophil-Directed Biological Therapies","volume":"39","author":"Jacobsen","year":"2021","journal-title":"Annu. Rev. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"AlBloushi, S., and Al-Ahmad, M. (2024). Exploring the immunopathology of type 2 inflammatory airway diseases. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1285598"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.crimmu.2022.03.002","article-title":"The emerging roles of eosinophils: Implications for the targeted treatment of eosinophilic-associated inflammatory conditions","volume":"3","author":"Lombardi","year":"2022","journal-title":"Curr. Res. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Mukherjee, M., Lacy, P., and Ueki, S. (2018). Eosinophil extracellular traps and inflammatory pathologies-untangling the web!. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02763"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.tcb.2026.03.010","article-title":"Eosinophil extracellular traps: Heterogeneity of their stimuli, components, and functions","volume":"36","author":"Zhang","year":"2026","journal-title":"Trends Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Fettrelet, T., Gigon, L., Karaulov, A., Yousefi, S., and Simon, H.U. (2021). The Enigma of Eosinophil Degranulation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22137091"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1136\/gutjnl-2023-330337","article-title":"Mepolizumab for treatment of adolescents and adults with eosinophilic oesophagitis: A multicentre, randomised, double-blind, placebo-controlled clinical trial","volume":"72","author":"Dellon","year":"2023","journal-title":"Gut"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1016\/j.jaci.2013.11.024","article-title":"Electron microscopy elucidates eosinophil degranulation patterns in patients with eosinophilic esophagitis","volume":"133","author":"Saffari","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1056\/NEJMra2032506","article-title":"Biologic Therapies for Severe Asthma","volume":"386","author":"Brusselle","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.jaci.2020.04.040","article-title":"Type 2 inflammation in chronic rhinosinusitis without nasal polyps: Another relevant endotype","volume":"146","author":"Delemarre","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1016\/S0140-6736(25)01625-3","article-title":"Anti-cytokine biologics for asthma in adults","volume":"406","author":"Israel","year":"2025","journal-title":"Lancet"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1182\/blood.V72.1.150.150","article-title":"Ultrastructural localization of the Charcot-Leyden crystal protein (lysophospholipase) to a distinct crystalloid-free granule population in mature human eosinophils","volume":"72","author":"Dvorak","year":"1988","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/JLB.3AB0220-311R","article-title":"Galectin-10, the protein that forms Charcot-Leyden crystals, is not stored in granules but resides in the peripheral cytoplasm of human eosinophils","volume":"108","author":"Melo","year":"2020","journal-title":"J. Leukoc. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1177\/42.11.7930526","article-title":"Ultrastructural localization of major basic protein in the human eosinophil lineage in vitro","volume":"42","author":"Dvorak","year":"1994","journal-title":"J. Histochem. Cytochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/labinvest.2009.40","article-title":"Vesicle-mediated secretion of human eosinophil granule-derived major basic protein","volume":"89","author":"Melo","year":"2009","journal-title":"Lab. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Davoine, F., and Lacy, P. (2014). Eosinophil cytokines, chemokines, and growth factors: Emerging roles in immunity. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00570"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/JLB.3MR1217-476R","article-title":"Contemporary understanding of the secretory granules in human eosinophils","volume":"104","author":"Melo","year":"2018","journal-title":"J. Leukoc. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1093\/jleuko\/qiae079","article-title":"Extracellular sombrero vesicles are hallmarks of eosinophilic cytolytic degranulation in tissue sites of human diseases","volume":"116","author":"Neves","year":"2024","journal-title":"J. Leukoc. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0065-2776(08)60351-X","article-title":"The eosinophilic leukocyte: Structure and function","volume":"39","author":"Gleich","year":"1986","journal-title":"Adv. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1111\/j.1600-0854.2005.00322.x","article-title":"Intragranular vesiculotubular compartments are involved in piecemeal degranulation by activated human eosinophils","volume":"6","author":"Melo","year":"2005","journal-title":"Traffic"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1111\/j.1600-0854.2005.00344.x","article-title":"Human eosinophils secrete preformed, granule-stored interleukin-4 through distinct vesicular compartments","volume":"6","author":"Melo","year":"2005","journal-title":"Traffic"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1189\/jlb.0707503","article-title":"Mechanisms of eosinophil secretion: Large vesiculotubular carriers mediate transport and release of granule-derived cytokines and other proteins","volume":"83","author":"Melo","year":"2008","journal-title":"J. Leukoc. Biol."},{"key":"ref_36","first-page":"1341","article-title":"Piecemeal degranulation in human eosinophils: A distinct secretion mechanism underlying inflammatory responses","volume":"25","author":"Melo","year":"2010","journal-title":"Histol. Histopath"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2813","DOI":"10.1172\/JCI117986","article-title":"Allergen-specific IgG1 and IgG3 through Fc gamma RII induce eosinophil degranulation","volume":"95","author":"Kaneko","year":"1995","journal-title":"J. Clin. Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6327","DOI":"10.4049\/jimmunol.0904043","article-title":"Mouse and human eosinophils degranulate in response to platelet-activating factor (PAF) and lysoPAF via a PAF-receptor-independent mechanism: Evidence for a novel receptor","volume":"184","author":"Dyer","year":"2010","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1002\/JLB.2MA0820-320RR","article-title":"Cytokine trafficking of IL-9 and IL-13 through TfnRc+ vesicles in activated human eosinophils","volume":"109","author":"Almas","year":"2020","journal-title":"J. Leukoc. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1189\/jlb.3A1015-480R","article-title":"CD63 is tightly associated with intracellular, secretory events chaperoning piecemeal degranulation and compound exocytosis in human eosinophils","volume":"100","author":"Carmo","year":"2016","journal-title":"J. Leukoc. Biol."},{"key":"ref_41","unstructured":"Lee, J.J., and Rosenberg, H.F. (2013). Signaling and Degranulation. Eosinophils in Health and Disease, Elsevier."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1182\/blood-2012-05-432088","article-title":"Eosinophil extracellular DNA trap cell death mediates lytic release of free secretion-competent eosinophil granules in humans","volume":"121","author":"Ueki","year":"2013","journal-title":"Blood"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1016\/j.jaci.2017.01.044","article-title":"Adhesion-induced eosinophil cytolysis requires the receptor-interacting protein kinase 3 (RIPK3)-mixed lineage kinase-like (MLKL) signaling pathway, which is counterregulated by autophagy","volume":"140","author":"Wang","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1016\/j.jaci.2014.11.026","article-title":"Exosome secretion by eosinophils: A possible role in asthma pathogenesis","volume":"135","author":"Mazzeo","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1084\/jem.171.3.775","article-title":"Intracellular application of guanosine-5\u2032-O-(3-thiotriphosphate) induces exocytotic granule fusion in guinea pig eosinophils","volume":"171","author":"Nusse","year":"1990","journal-title":"J. Exp. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.4049\/jimmunol.147.6.1905","article-title":"Mechanisms of granule enzyme secretion from permeabilized guinea pig eosinophils. Dependence on Ca2+ and guanine nucleotides","volume":"147","author":"Cromwell","year":"1991","journal-title":"J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1159\/000322597","article-title":"Agonist activation of f-actin-mediated eosinophil shape change and mediator release is dependent on Rac2","volume":"156","author":"Lacy","year":"2011","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.4049\/jimmunol.135.2.1349","article-title":"Calcium ionophore A23187 calcium-dependent cytolytic degranulation in human eosinophils","volume":"135","author":"Fukuda","year":"1985","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1002\/j.1460-2075.1993.tb05829.x","article-title":"Focal exocytosis by eosinophils\u2014Compound exocytosis and cumulative fusion","volume":"12","author":"Scepek","year":"1993","journal-title":"EMBO J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/0091-6749(92)90103-9","article-title":"Induction of granule release by intracellular application of calcium and guanosine-5\u2032-O-(3-thiotriphosphate) in human eosinophils","volume":"90","author":"Aizawa","year":"1992","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1242\/jcs.104.1.203","article-title":"The membrane fusion events in degranulating guinea pig eosinophils","volume":"104","author":"Lindau","year":"1993","journal-title":"J. Cell Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3159","DOI":"10.1111\/all.14450","article-title":"Lysophosphatidylserine induces eosinophil extracellular trap formation and degranulation: Implications in severe asthma","volume":"75","author":"Kim","year":"2020","journal-title":"Allergy"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1007\/s10753-011-9309-5","article-title":"PI3-kinase regulates eosinophil and neutrophil degranulation in patients with allergic rhinitis and allergic asthma irrespective of allergen challenge model","volume":"35","author":"Kampe","year":"2012","journal-title":"Inflammation"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Knuplez, E., Sturm, E.M., and Marsche, G. (2021). Emerging Role of Phospholipase-Derived Cleavage Products in Regulating Eosinophil Activity: Focus on Lysophospholipids, Polyunsaturated Fatty Acids and Eicosanoids. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094356"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/j.1365-2567.2005.02210.x","article-title":"An atypical protein kinase C, PKC zeta, regulates human eosinophil effector functions","volume":"116","author":"Kato","year":"2005","journal-title":"Immunology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.jaci.2015.04.041","article-title":"Eosinophil extracellular trap cell death-derived DNA traps: Their presence in secretions and functional attributes","volume":"137","author":"Ueki","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1182\/blood.V96.7.2506","article-title":"Syk-deficient eosinophils show normal interleukin-5-mediated differentiation, maturation, and survival but no longer respond to FcgammaR activation","volume":"96","author":"Menear","year":"2000","journal-title":"Blood"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0092-8674(00)80727-8","article-title":"SNARE complex formation is triggered by Ca2+ and drives membrane fusion","volume":"97","author":"Chen","year":"1999","journal-title":"Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1152\/physrev.2000.80.2.717","article-title":"Neurotoxins affecting neuroexocytosis","volume":"80","author":"Schiavo","year":"2000","journal-title":"Physiol. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1083\/jcb.132.1.167","article-title":"VAMP\/synaptobrevin isoforms 1 and 2 are widely and differentially expressed in nonneuronal tissues","volume":"132","author":"Rossetto","year":"1996","journal-title":"J. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1006\/bbrc.2000.2591","article-title":"Rat basophilic leukemia cells express syntaxin-3 and VAMP-7 in granule membranes","volume":"271","author":"Hibi","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"13300","DOI":"10.1074\/jbc.271.23.13300","article-title":"Identification of a novel syntaxin- and synaptobrevin\/VAMP-binding protein, SNAP-23, expressed in non-neuronal tissues","volume":"271","author":"Ravichandran","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1091\/mbc.9.6.1437","article-title":"A novel tetanus neurotoxin-insensitive vesicle-associated membrane protein in SNARE complexes of the apical plasma membrane of epithelial cells","volume":"9","author":"Galli","year":"1998","journal-title":"Mol. Biol. Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.1091\/mbc.11.9.3137","article-title":"Syntaxin 7 is localized to late endosome compartments, associates with Vamp 8, and Is required for late endosome-lysosome fusion","volume":"11","author":"Mullock","year":"2000","journal-title":"Mol. Biol. Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"44921","DOI":"10.1074\/jbc.M306013200","article-title":"Compound exocytosis and cumulative fusion in eosinophils","volume":"278","author":"Hafez","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/rr8","article-title":"Phosphoinositide 3-kinase: A critical signalling event in pulmonary cells","volume":"1","author":"Condliffe","year":"2000","journal-title":"Respir. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"173353","DOI":"10.1016\/j.ejphar.2020.173353","article-title":"Functional role of phosphatidylcholine-specific phospholipase C in regulating leukotriene synthesis and degranulation in human eosinophils","volume":"884","author":"Sano","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/j.1748-1716.2011.02298.x","article-title":"Mammalian phospholipase D physiological and pathological roles","volume":"204","author":"Peng","year":"2012","journal-title":"Acta Physiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1111\/cea.13538","article-title":"Eosinophil cytolysis on Immunoglobulin G is associated with microtubule formation and suppression of rho-associated protein kinase signalling","volume":"50","author":"Esnault","year":"2020","journal-title":"Clin. Exp. Allergy"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"245","DOI":"10.2332\/allergolint.55.245","article-title":"Role of protein kinase C in eosinophil function","volume":"55","author":"Yamaguchi","year":"2006","journal-title":"Allergol. Int. Off. J. Jpn. Soc. Allergol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1182\/blood.V95.6.1911","article-title":"Eotaxin induces degranulation and chemotaxis of eosinophils through the activation of ERK2 and p38 mitogen-activated protein kinases","volume":"95","author":"Kampen","year":"2000","journal-title":"Blood"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1159\/000070476","article-title":"Distinct isoforms of protein kinase C are involved in human eosinophil functions induced by platelet-activating factor","volume":"131","author":"Takizawa","year":"2003","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1111\/all.12163","article-title":"PI3K, ERK, p38 MAPK and integrins regulate CCR3-mediated secretion of mouse and human eosinophil-associated RNases","volume":"68","author":"Shamri","year":"2013","journal-title":"Allergy"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1111\/imm.12416","article-title":"Cyclin-Dependent Kinase 5 Regulates Degranulation in Human Eosinophils","volume":"144","author":"Odemuyiwa","year":"2014","journal-title":"Immunology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/35074516","article-title":"ERK induces p35, a neuron-specific activator of Cdk5, through induction of Egr1","volume":"3","author":"Harada","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.alit.2020.10.002","article-title":"How to detect eosinophil ETosis (EETosis) and extracellular traps","volume":"70","author":"Fukuchi","year":"2021","journal-title":"Allergol. Int. Off. J. Jpn. Soc. Allergol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1182\/blood-2018-04-842260","article-title":"Charcot-Leyden crystal formation is closely associated with eosinophil extracellular trap cell death","volume":"132","author":"Ueki","year":"2018","journal-title":"Blood"},{"key":"ref_78","first-page":"14","article-title":"Role of tyrosine kinases in human eosinophil degranulation","volume":"114","author":"Kato","year":"1997","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1084\/jem.188.3.421","article-title":"Lyn, Jak2, and Raf-1 kinases are critical for the antiapoptotic effect of interleukin 5, whereas only Raf-1 kinase is essential for eosinophil activation and degranulation","volume":"188","author":"Pazdrak","year":"1998","journal-title":"J. Exp. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.4049\/jimmunol.168.4.1978","article-title":"Lyn tyrosine kinase is important for IL-5-stimulated eosinophil differentiation","volume":"168","author":"Stafford","year":"2002","journal-title":"J. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1006\/bbrc.1999.1379","article-title":"Novel association of the src family kinases, hck and c-fgr, with CCR3 receptor stimulation: A possible mechanism for eotaxin-induced human eosinophil chemotaxis","volume":"264","author":"Yamaguchi","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/79767","article-title":"Regulation of tyrosine kinase activation and granule release through b-arrestin by CXCRI","volume":"1","author":"Barlic","year":"2000","journal-title":"Nat. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Xue, R., Meng, H., Yin, J., Xia, J., Hu, Z., and Liu, H. (2021). The Role of Calmodulin vs. Synaptotagmin in Exocytosis. Front. Mol. Neurosci., 14.","DOI":"10.3389\/fnmol.2021.691363"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"6379","DOI":"10.1016\/j.cell.2024.08.017","article-title":"Targeting Ras-, Rho-, and Rab-family GTPases via a conserved cryptic pocket","volume":"187","author":"Morstein","year":"2024","journal-title":"Cell"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3547","DOI":"10.1242\/jcs.108.11.3547","article-title":"A survey of GTP-binding proteins and other potential key regulators of exocytotic secretion in eosinophils: Apparent absence of rab3 and vesicle fusion protein homologues","volume":"108","author":"Lacy","year":"1995","journal-title":"J. Cell Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1021\/acs.jproteome.6b00006","article-title":"The Peripheral Blood Eosinophil Proteome","volume":"15","author":"Wilkerson","year":"2016","journal-title":"J. Proteome Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1189\/jlb.0812431","article-title":"An essential role for Rab27a GTPase in eosinophil exocytosis","volume":"94","author":"Kim","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"7879","DOI":"10.4049\/jimmunol.178.12.7879","article-title":"Coexpression of IL-5 and eotaxin-2 in mice creates an eosinophil-dependent model of respiratory inflammation with characteristics of severe asthma","volume":"178","author":"Ochkur","year":"2007","journal-title":"J. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e70091","DOI":"10.1002\/iid3.70091","article-title":"The Immunosuppressive Functions of Eosinophils Are Compromised in Patients with Allergic Rhinitis, Particularly Concerning Rab27a Expression","volume":"12","author":"Liao","year":"2024","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1242\/jcs.01118","article-title":"Rho-family GTPases: It\u2019s not only Rac and Rho (and I like it)","volume":"117","author":"Wennerberg","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/nature01148","article-title":"Rho GTPases in cell biology","volume":"420","author":"Hall","year":"2002","journal-title":"Nature"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-61779-442-1_1","article-title":"Historical overview of Rho GTPases","volume":"827","author":"Ridley","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/362318a0","article-title":"SNAP receptors implicated in vesicle targeting and fusion","volume":"362","author":"Sollner","year":"1993","journal-title":"Nature"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/26412","article-title":"Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 A resolution","volume":"395","author":"Sutton","year":"1998","journal-title":"Nature"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41580-023-00668-x","article-title":"Mechanisms of SNARE proteins in membrane fusion","volume":"25","author":"Jahn","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1091\/mbc.11.7.2327","article-title":"Syntaxin 7 and VAMP-7 are soluble N-ethylmaleimide-sensitive factor attachment protein receptors required for late endosome-lysosome and homotypic lysosome fusion in alveolar macrophages","volume":"11","author":"Ward","year":"2000","journal-title":"Mol. Biol. Cell"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1083\/jcb.146.4.765","article-title":"VAMP-7 mediates vesicular transport from endosomes to lysosomes","volume":"146","author":"Advani","year":"1999","journal-title":"J. Cell Biol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"5850","DOI":"10.4049\/jimmunol.164.11.5850","article-title":"Soluble NSF attachment protein receptors (SNAREs) in RBL-2H3 mast cells: Functional role of syntaxin 4 in exocytosis and identification of a vesicle-associated membrane protein 8-containing secretory compartment","volume":"164","author":"Paumet","year":"2000","journal-title":"J. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1182\/blood.V100.3.1081","article-title":"Vesicle-associated membrane protein 3 (VAMP-3) and VAMP-8 are present in human platelets and are required for granule secretion","volume":"100","author":"Polgar","year":"2002","journal-title":"Blood"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1006\/bbrc.2001.4499","article-title":"SNARE proteins are critical for regulated exocytosis of ECP from human eosinophils","volume":"282","author":"Hoffmann","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1067\/mai.2001.113562","article-title":"Fusion protein vesicle-associated membrane protein 2 is implicated in IFN-gamma-induced piecemeal degranulation in human eosinophils from atopic individuals","volume":"107","author":"Lacy","year":"2001","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1067\/mai.2002.121453","article-title":"Expression of eosinophil target SNAREs as potential cognate receptors for vesicle-associated membrane protein-2 in exocytosis","volume":"109","author":"Logan","year":"2002","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1111\/j.1398-9995.2006.01089.x","article-title":"A critical role for vesicle-associated membrane protein-7 in exocytosis from human eosinophils and neutrophils","volume":"61","author":"Logan","year":"2006","journal-title":"Allergy"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.yexcr.2015.07.003","article-title":"Expression and subcellular localization of the Qa-SNARE syntaxin17 in human eosinophils","volume":"337","author":"Carmo","year":"2015","journal-title":"Exp. Cell Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.bbrc.2007.11.079","article-title":"Vesicle-associated membrane protein 7 (VAMP-7) is essential for target cell killing in a natural killer cell line","volume":"366","author":"Odemuyiwa","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/s42003-018-0081-z","article-title":"Vesicle-associated membrane protein 7-mediated eosinophil degranulation promotes allergic airway inflammation in mice","volume":"1","author":"Willetts","year":"2018","journal-title":"Commun. Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1189\/jlb.0213089","article-title":"Homologous recombination into the eosinophil peroxidase locus generates a strain of mice expressing Cre recombinase exclusively in eosinophils","volume":"94","author":"Doyle","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Gigon, L., Fettrelet, T., Miholic, M., McLeish, K.R., Yousefi, S., Stojkov, D., and Simon, H.U. (2023). Syntaxin-4 and SNAP23 are involved in neutrophil degranulation, but not in the release of mitochondrial DNA during NET formation. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1272699"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1002\/cbf.3740","article-title":"ATG5: A central autophagy regulator implicated in various human diseases","volume":"40","author":"Changotra","year":"2022","journal-title":"Cell Biochem. Funct."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2958","DOI":"10.1182\/blood.2020010208","article-title":"ATG5 promotes eosinopoiesis but inhibits eosinophil effector functions","volume":"137","author":"Germic","year":"2021","journal-title":"Blood"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/nature11320","article-title":"Molecular machines governing exocytosis of synaptic vesicles","volume":"490","author":"Jahn","year":"2012","journal-title":"Nature"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/j.bbamcr.2006.09.004","article-title":"Exocytosis in neuroendocrine cells: New tasks for actin","volume":"1763","author":"Malacombe","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"17406","DOI":"10.1074\/jbc.R113.546218","article-title":"Eosinophil granule proteins: Form and function","volume":"289","author":"Acharya","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s40413-016-0112-5","article-title":"Eosinophilic bioactivities in severe asthma","volume":"9","author":"Carr","year":"2016","journal-title":"World Allergy Organ. J."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.jaci.2024.03.023","article-title":"Utility of eosinophil peroxidase as a biomarker of eosinophilic inflammation in asthma","volume":"154","author":"Tang","year":"2024","journal-title":"J. Allergy Clin. Immunol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/13\/1211\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T10:44:23Z","timestamp":1783075463000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/13\/1211"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,3]]},"references-count":115,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["cells15131211"],"URL":"https:\/\/doi.org\/10.3390\/cells15131211","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,3]]}}}