{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T16:53:47Z","timestamp":1759683227355,"version":"3.38.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology","doi-asserted-by":"publisher","award":["EMR\/2016\/001880"],"award-info":[{"award-number":["EMR\/2016\/001880"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research","doi-asserted-by":"publisher","award":["UNDO","SPLenDID"],"award-info":[{"award-number":["UNDO","SPLenDID"]}],"id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Eosinophils mediate pathological manifestations during tropical pulmonary eosinophilia (TPE), a potentially fatal complication of lymphatic filariasis, by mechanisms that are incompletely understood. Using two-dimensional gel electrophoresis, mass spectrometry, flow cytometry, and pharmacological and functional studies, we identified acidic calcium-independent phospholipase A2 (aiPLA2) as the master regulator of TPE pathogenesis. FACS-sorted lung eosinophils from TPE mice exhibited aiPLA2-dependent activation characterized by heavy calcium influx, F-actin polymerization, increased degranulation, and heightened reactive oxygen species generation. Interestingly, aiPLA2 also promoted alternative activation in lung macrophages and regulated the release of inflammatory intermediates from them. Treatment of TPE mice with MJ33, a nontoxic pharmacological inhibitor of aiPLA2, lowered eosinophil counts in the bronchoalveolar lavage fluid, reduced eosinophil peroxidase and \u03b2-hexosaminidase activity, increased airway width, improved lung endothelial barrier, and lowered the production of inflammatory lipid intermediates, which significantly improved the pathological condition of the lungs. Importantly, ex vivo reconstitution of arachidonic acid to eosinophils from MJ33-treated TPE mice increased eosinophil degranulation and inflammatory lipid intermediates underlining the pivotal role of aiPLA2 in arachidonic acid metabolism. Mechanistically, phosphorylation of JNK-1 regulated phospholipase activity of aiPLA2, whereas IgG cross-linking mediated pathological activation of eosinophils. Taken together, ours is the first study, to our knowledge, to report hitherto undocumented role of aiPLA2 in regulating TPE pathogenesis.<\/jats:p>","DOI":"10.4049\/jimmunol.2000604","type":"journal-article","created":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T18:32:20Z","timestamp":1610562740000},"page":"722-736","source":"Crossref","is-referenced-by-count":7,"title":["Acidic Calcium-Independent Phospholipase A2 Regulates Eosinophil-Mediated Pathology during Filarial Manifestation of Tropical Pulmonary Eosinophilia"],"prefix":"10.1093","volume":"206","author":[{"given":"Pankaj","family":"Sharma","sequence":"first","affiliation":[{"name":"Molecular Parasitology and Immunology Division, Council of Scientific and Industrial Research-Central Drug Research Institute , Lucknow 226031 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7199-0361","authenticated-orcid":false,"given":"Aditi","family":"Sharma","sequence":"additional","affiliation":[{"name":"Molecular Parasitology and Immunology Division, Council of Scientific and Industrial Research-Central Drug Research Institute , Lucknow 226031 ,","place":["India"]},{"name":"Academy of Scientific and Innovative Research , Ghaziabad 201002 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laxmi","family":"Ganga","sequence":"additional","affiliation":[{"name":"Molecular Parasitology and Immunology Division, Council of Scientific and Industrial Research-Central Drug Research Institute , Lucknow 226031 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neha","family":"Satoeya","sequence":"additional","affiliation":[{"name":"Molecular Parasitology and Immunology Division, Council of Scientific and Industrial Research-Central Drug Research Institute , Lucknow 226031 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruchi","family":"Jha","sequence":"additional","affiliation":[{"name":"Molecular Parasitology and Immunology Division, Council of Scientific and Industrial Research-Central Drug Research Institute , Lucknow 226031 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9324-7843","authenticated-orcid":false,"given":"Mrigank","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Molecular Parasitology and Immunology Division, Council of Scientific and Industrial Research-Central Drug Research Institute , Lucknow 226031 ,","place":["India"]},{"name":"Academy of Scientific and Innovative Research , Ghaziabad 201002 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,2,15]]},"reference":[{"key":"2025030501510186600_r1","first-page":"295","article-title":"Tropical pulmonary eosinophilia--a review","volume":"138","author":"Mullerpattan","year":"2013","journal-title":"Indian J. 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