{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:47:34Z","timestamp":1790628454536,"version":"4.1.0"},"reference-count":48,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T00:00:00Z","timestamp":1686268800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["308390\/2021-0"],"award-info":[{"award-number":["308390\/2021-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The systemic increase in inflammatory mediator levels can induce diverse pathological disorders, including potentially thrombus formation, which may be lethal. Among the clinical conditions in which the formation of thrombi dictates the patient\u2019s prognosis, envenomation by Bothrops lanceolatus should be emphasized, as it can evolve to stroke, myocardial infarction and pulmonary embolism. Despite their life-threatening potential, the immunopathological events and toxins involved in these reactions remain poorly explored. Therefore, in the present study, we examined the immunopathological events triggered by a PLA2 purified from B. lanceolatus venom, using an ex vivo human blood model of inflammation. Our results showed that the purified PLA2 from the venom of B. lanceolatus damages human erythrocytes in a dose dependent way. The cell injury was associated with a decrease in the levels of CD55 and CD59 complement regulators on the cell surface. Moreover, the generation of anaphylatoxins (C3a and C5a) and the soluble terminal complement complex (sTCC) indicates that human blood exposure to the toxin activates the complement system. Increased production of TNF-\u03b1, CXCL8, CCL2 and CCL5 followed complement activation. The venom PLA2 also triggered the generation of lipid mediators, as evidenced by the detected high levels of LTB4, PGE2 and TXB2. The scenario here observed of red blood cell damage, dysfunctions of the complement regulatory proteins, accompanied by an inflammatory mediator storm, suggests that B. lanceolatus venom PLA2 contributes to the thrombotic disorders present in the envenomed individuals.<\/jats:p>","DOI":"10.3390\/ijms24129931","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T02:59:57Z","timestamp":1686279597000},"page":"9931","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["New Insights into Immunopathology Associated to Bothrops lanceolatus Snake Envenomation: Focus on PLA2 Toxin"],"prefix":"10.3390","volume":"24","author":[{"given":"Joel J. M.","family":"Gabrili","sequence":"first","affiliation":[{"name":"Immunochemistry Laboratory, Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giselle","family":"Pidde","sequence":"additional","affiliation":[{"name":"Immunochemistry Laboratory, Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio Carlos","family":"Magnoli","sequence":"additional","affiliation":[{"name":"Immunochemistry Laboratory, Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Marques-Porto","sequence":"additional","affiliation":[{"name":"Development and Innovation Laboratory, Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isadora Maria","family":"Villas-Boas","sequence":"additional","affiliation":[{"name":"Immunochemistry Laboratory, Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4187-798X","authenticated-orcid":false,"given":"Carla Cristina","family":"Squaiella-Baptist\u00e3o","sequence":"additional","affiliation":[{"name":"Immunochemistry Laboratory, Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Silva-de-Fran\u00e7a","sequence":"additional","affiliation":[{"name":"Immunochemistry Laboratory, Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Burgher","sequence":"additional","affiliation":[{"name":"Prevor Laboratory, 95760 Valmondois, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00ebl","family":"Blomet","sequence":"additional","affiliation":[{"name":"Prevor Laboratory, 95760 Valmondois, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1896-9074","authenticated-orcid":false,"given":"Denise V.","family":"Tambourgi","sequence":"additional","affiliation":[{"name":"Immunochemistry Laboratory, Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"},{"name":"Prevor Laboratory, 95760 Valmondois, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3390\/toxins2010163","article-title":"Bothrops lanceolatus bites: Guidelines for severity assessment and emergent management","volume":"2","author":"Resiere","year":"2010","journal-title":"Toxins"},{"key":"ref_2","unstructured":"Cardoso, J.L.C. 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