{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T05:53:17Z","timestamp":1792389197563,"version":"4.4.0"},"reference-count":51,"publisher":"Portland Press Ltd.","issue":"5","license":[{"start":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T00:00:00Z","timestamp":1614038400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,3,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Muscle tissue damage is one of the local effects described in bothropic envenomations. Bothropstoxin-I (BthTX-I), from Bothrops jararacussu venom, is a K49-phospholipase A2 (PLA2) that induces a massive muscle tissue injury, and, consequently, local inflammatory reaction. The NLRP3 inflammasome is a sensor that triggers inflammation by activating caspase 1 and releasing interleukin (IL)-1\u03b2 and\/or inducing pyroptotic cell death in response to tissue damage. We, therefore, aimed to address activation of NLRP3 inflammasome by BthTX-I-associated injury and the mechanism involved in this process. Intramuscular injection of BthTX-I results in infiltration of neutrophils and macrophages in gastrocnemius muscle, which is reduced in NLRP3- and Caspase-1-deficient mice. The in vitro IL-1\u03b2 production induced by BthTX-I in peritoneal macrophages (PMs) requires caspase 1\/11, ASC and NLRP3 and is dependent on adenosine 5\u2032-triphosphate (ATP)-induced K+ efflux and P2X7 receptor (P2X7R). BthTX-I induces a dramatic release of ATP from C2C12 myotubes, therefore representing the major mechanism for P2X7R-dependent inflammasome activation in macrophages. A similar result was obtained when human monocyte-derived macrophages (HMDMs) were treated with BthTX-I. These findings demonstrated the inflammatory effect of BthTX-I on muscle tissue, pointing out a role for the ATP released by damaged cells for the NLRP3 activation on macrophages, contributing to the understanding of the microenvironment of the tissue damage of the Bothrops envenomation.<\/jats:p>","DOI":"10.1042\/cs20201419","type":"journal-article","created":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T13:01:52Z","timestamp":1614085312000},"page":"687-701","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Inflammatory effect of Bothropstoxin-I from <i>Bothrops jararacussu<\/i> venom mediated by NLRP3 inflammasome involves ATP and P2X7 receptor"],"prefix":"10.1042","volume":"135","author":[{"given":"Priscila Andrade","family":"Ran\u00e9ia e Silva","sequence":"first","affiliation":[{"name":"Laboratory of Immunopathology, Butantan Institute, S\u00e3o Paulo, Brazil"},{"name":"Department of Immunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dh\u00eamerson Souza","family":"de Lima","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Paulo","family":"Mesquita Luiz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Department of Immunology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels Olsen Saraiva","family":"C\u00e2mara","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Carlos Farias","family":"Alves-Filho","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Department of Immunology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Pontillo","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina Ramalho","family":"Bortoluci","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Center for Cellular and Molecular Therapy (CTC-Mol),Federal University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8083-4272","authenticated-orcid":false,"given":"Eliana L.","family":"Faquim-Mauro","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopathology, Butantan Institute, S\u00e3o Paulo, Brazil"},{"name":"Department of Immunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2021,3,9]]},"reference":[{"key":"2021113011195555800_B1","first-page":"315","article-title":"Randomized comparative trial of three antivenoms in the treatment of envenoming by lance-headed vipers (Bothrops jararaca) in S\u00e3o Paulo, Brazil","volume":"86","author":"Cardoso","year":"1993","journal-title":"Q J Med."},{"key":"2021113011195555800_B2","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1016\/j.toxicon.2012.02.008","article-title":"Improving antivenom availability and accessibility: science, technology, and beyond","volume":"60","author":"Guti\u00e9rrez","year":"2012","journal-title":"Toxicon"},{"key":"2021113011195555800_B3","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/S0140-6736(09)61159-4","article-title":"The Global Snake Bite Initiative: an antidote for snake bite","volume":"375","author":"Williams","year":"2010","journal-title":"Lancet"},{"key":"2021113011195555800_B4","doi-asserted-by":"publisher","first-page":"5120","DOI":"10.1021\/pr900489m","article-title":"Wound exudate as a proteomic window to reveal different mechanisms of tissue damage by snake venom toxins","volume":"8","author":"Escalante","year":"2009","journal-title":"J. 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