{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T23:55:18Z","timestamp":1781654118790,"version":"3.54.5"},"reference-count":36,"publisher":"Georg Thieme Verlag KG","issue":"CP","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Medical and Health Science and Technology Program of Zhejiang Province","award":["2024KY1064"],"award-info":[{"award-number":["2024KY1064"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TH Open"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Platelets and certain immune cells contain releasable granules that play essential roles in hemostasis and immune regulation. However, the regulatory mechanisms governing degranulation of platelets versus immune cells remain incompletely understood.<\/jats:p>\n                  <jats:p>This study aimed to elucidate the distinct regulatory mechanisms underlying granule release in platelets and immune cells.<\/jats:p>\n                  <jats:p>Mouse platelets were freshly isolated from peripheral blood, neutrophils were purified from bone marrow, and mast cells were generated from bone marrow progenitors by in vitro differentiation. The effects of phorbol ester (PMA), ionomycin, and their combination on degranulation of platelets, neutrophils, and mast cells were examined. In addition, pharmacological inhibitors targeting key components of multiple signaling pathways were used to investigate the molecular mechanisms regulating degranulation of these three cell types.<\/jats:p>\n                  <jats:p>PMA and ionomycin strongly induced \u03b1-granule release of platelets, whereas only moderately stimulating dense-granule secretion. For neutrophils, PMA and ionomycin each triggered moderate azurophilic-granule release, whereas their combination markedly enhanced degranulation. In contrast, PMA alone failed to induce mast cell degranulation, ionomycin robustly stimulated granule release, and their combination further amplified ionomycin-induced response. Mechanistically, thrombin-induced platelet degranulation was inhibited exclusively by phospholipase C (PLC) and protein kinase C (PKC) inhibitors. Zymosan-induced neutrophil degranulation was suppressed by inhibitors of phosphoinositide 3 kinase, spleen tyrosine kinase (SYK), Bruton's tyrosine kinase (BTK), mitogen-activated protein kinase 1\/2 (MEK1\/2) and P38 but was enhanced by PLC and PKC inhibition. Mast cell degranulation induced by IgE and antigen was significantly inhibited by the inhibitors targeting SYK, BTK, PLC, and PKC.<\/jats:p>\n                  <jats:p>These findings reveal substantial differences in the regulatory pathways controlling degranulation in platelets and immune cells. Such distinctions highlight the opportunities for the development of cell type-selective inhibitors to modulate degranulation, providing potential therapeutic strategies for thrombotic diseases and immune-related diseases.<\/jats:p>","DOI":"10.1055\/a-2885-2208","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T23:21:32Z","timestamp":1781652092000},"source":"Crossref","is-referenced-by-count":0,"special_numbering":"S","title":["Differential Regulation of Granule Release in Platelets and Immune Cells"],"prefix":"10.1055","volume":"10","author":[{"given":"Qing","family":"Xia","sequence":"additional","affiliation":[{"name":"The Affiliated People's Hospital of Ningbo University, Zhejiang, China","place":["Ningbo"],"department":["Department of Hematology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiandao","family":"Hu","sequence":"additional","affiliation":[{"name":"The Affiliated People's Hospital of Ningbo University, Zhejiang, China","place":["Ningbo"],"department":["Department of Otolaryngology\u2013Head and Neck Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongcun","family":"Sun","sequence":"additional","affiliation":[{"name":"The Affiliated People's Hospital of Ningbo University, Zhejiang, China","place":["Ningbo"],"department":["Department of Otolaryngology\u2013Head and Neck Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7476-309X","authenticated-orcid":false,"given":"Zhixiang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, China","place":["Beijing"],"department":["Modern Research Center for Traditional Chinese Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8012-1544","authenticated-orcid":false,"given":"Wenbo","family":"Jiang","sequence":"additional","affiliation":[{"name":"The Affiliated People's Hospital of Ningbo University, Zhejiang, China","place":["Ningbo"],"department":["Department of Otolaryngology\u2013Head and Neck Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"issue":"04","key":"ref1","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1080\/09537104.2021.1913576","article-title":"Release of \u03b1-granule contents during platelet activation","volume":"33","author":"C W Smith","year":"2022","journal-title":"Platelets"},{"issue":"14","key":"ref2","doi-asserted-by":"crossref","first-page":"3258","DOI":"10.1182\/bloodadvances.2020002117","article-title":"Platelet \u03b1-granules are required for occlusive high-shear-rate 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