{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T20:49:53Z","timestamp":1791838193781,"version":"4.3.4"},"reference-count":92,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24gm1210013"],"award-info":[{"award-number":["24gm1210013"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Lipids play fundamental roles in life. In essence, \u201cphospholipase A2\u201d (PLA2) indicates a group of enzymes that release fatty acids and lysophospholipids by hydrolyzing the sn-2 position of glycerophospholipids. To date, more than 50 enzymes that possess PLA2 or related lipid-metabolizing activities have been identified in mammals and are subdivided into several families in terms of their structures, catalytic mechanisms, tissue\/cellular localizations, and evolutionary relationships. Among the PLA2 superfamily, the secreted PLA2 (sPLA2) family contains 11 isoforms in mammals, each of which has unique substrate specificity and tissue\/cellular distributions. Recent studies using gene-manipulated (knockout and\/or transgenic) mice for a full set of sPLA2s have revealed their diverse roles in immunity, metabolism, and other biological events. Application of mass spectrometric lipidomics to these mice has allowed the identification of target substrates and products of individual sPLA2s in tissue microenvironments. In principle, sPLA2s hydrolyze extracellular phospholipids such as those in extracellular vesicles, microbes, lipoproteins, surfactants, and ingested foods, as well as phospholipids in the plasma membrane of activated or damaged cells, thereby exacerbating or ameliorating various diseases. The actions of sPLA2s are dependent on, or independent of, the generation of free fatty acids, lysophospholipids, or their metabolites (lipid mediators) according to pathophysiological contexts. In this review, I will make an overview of recent understanding of the unexplored immunoregulatory roles of sPLA2s and their underlying lipid pathways, especially focusing on their unique actions on extracellular vesicles, activated\/damaged cells, and gut microbiota.<\/jats:p>","DOI":"10.1093\/intimm\/dxaf027","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T08:06:42Z","timestamp":1747382802000},"page":"599-610","source":"Crossref","is-referenced-by-count":10,"title":["Secreted phospholipase A2 regulates intercellular communications by coordinating extracellular phospholipid metabolism"],"prefix":"10.1093","volume":"37","author":[{"given":"Makoto","family":"Murakami","sequence":"first","affiliation":[{"name":"Laboratory of Microenvironmental and Metabolic Health Science, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 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