Formyl peptide receptors are involved in CTX-induced impairment of lymphocyte functions.

Autor: Zambelli VO; Laboratory of Pain and Signaling, Butantan Institute, Av. Vital Brazil, 1500, 05503-900, São Paulo, SP, Brazil. Electronic address: vanessa.zambelli@butantan.gov.br., Hösch NG; Laboratory of Pain and Signaling, Butantan Institute, Av. Vital Brazil, 1500, 05503-900, São Paulo, SP, Brazil., Farom S; Laboratory of Pain and Signaling, Butantan Institute, Av. Vital Brazil, 1500, 05503-900, São Paulo, SP, Brazil; Laboratory of Pathophysiology, Butantan Institute, Av. Vital Brazil, 1500, 05503-900, São Paulo, SP, Brazil., Zychar BC; Laboratory of Pathophysiology, Butantan Institute, Av. Vital Brazil, 1500, 05503-900, São Paulo, SP, Brazil., Spadacci-Morena DD; Laboratory of Pathophysiology, Butantan Institute, Av. Vital Brazil, 1500, 05503-900, São Paulo, SP, Brazil., Carvalho LV; Laboratory of Immunochemistry, Butantan Institute, Av. Vital Brasil, 1500, 05503-900, São Paulo, SP, Brazil., Curi R; Immunobiological Production Section, Bioindustrial Center, Av. Vital Brazil, 1500, 05503-900, São Paulo, SP, Brazil; Interdisciplinary Post-graduate Program in Health Sciences, Cruzeiro of Sul University, São Paulo, SP, Brazil., Lepsch LB; Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, 05508-900, Brazil., Scavone C; Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, 05508-900, Brazil., Sant'Anna OA; Laboratory of Immunochemistry, Butantan Institute, Av. Vital Brasil, 1500, 05503-900, São Paulo, SP, Brazil., Gonçalves LRC; Laboratory of Pathophysiology, Butantan Institute, Av. Vital Brazil, 1500, 05503-900, São Paulo, SP, Brazil., Cury Y; Laboratory of Pain and Signaling, Butantan Institute, Av. Vital Brazil, 1500, 05503-900, São Paulo, SP, Brazil., Sampaio SC; Laboratory of Pathophysiology, Butantan Institute, Av. Vital Brazil, 1500, 05503-900, São Paulo, SP, Brazil. Electronic address: sandra.coccuzzo@butantan.gov.br.
Jazyk: angličtina
Zdroj: Toxicon : official journal of the International Society on Toxinology [Toxicon] 2023 Jan 15; Vol. 222, pp. 106986. Date of Electronic Publication: 2022 Nov 25.
DOI: 10.1016/j.toxicon.2022.106986
Abstrakt: Crotoxin (CTX) is a neurotoxin that is isolated from the venom of Crotalus durissus terrificus, which displays immunomodulatory, anti-inflammatory, and anti-tumoral effects. Previous research has demonstrated that CTX promotes the adherence of leukocytes to the endothelial cells in blood microcirculation and the high endothelial venules of lymph nodes, which reduces the number of blood cells and lymphocytes. Studies have also shown that these effects are mediated by lipoxygenase-derived mediators. However, the exact lipoxygenase-derived eicosanoid involved in the CTX effect on lymphocytes is yet to be characterized. As CTX stimulates lipoxin-derived mediators from macrophages and lymphocyte effector functions could be modulated by activating formyl peptide receptors, we aimed to investigate whether these receptors were involved in CTX-induced redistribution and functions of lymphocytes in rats. We used male Wistar rats treated with CTX to demonstrate that Boc2 (butoxycarbonyl-Phe-Leu-Phe-Leu-Phe), an antagonist of formyl peptide receptors, prevented CTX-induced decrease in the number of circulating lymphocytes and increased the expression of the lymphocyte adhesion molecule LFA1. CTX reduced the T and B lymphocyte functions, such as lymphocyte proliferation in response to the mitogen Concanavalin A and antibody production in response to BSA immunization, respectively, which was prevented by the administration of Boc2. Importantly, mesenteric lymph node lymphocytes from CTX-treated rats showed an increased release of 15-epi-LXA 4 . These results indicate that formyl peptide receptors mediate CTX-induced redistribution of lymphocytes and that 15-epi-LXA 4 is a key mediator of the immunosuppressive effects of CTX.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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