Crotoxin Isolated from Crotalus durissus terrificus Venom Modulates the Functional Activity of Dendritic Cells via Formyl Peptide Receptors

Autor(es)

Freitas, A. P. ; Favoretto, B. C. ; Clissa, P. B. ; Sampaio, S. C. ; Faquim-Mauro, E. L.

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF IMMUNOLOGY RESEARCH; v. 2018, p. 15-pg., 2018-01-01.

Resumo

The Crotalus durissus terrificus rattlesnake venom, its main toxin, crotoxin (CTX), and its crotapotin (CA) and phospholipase A(2) (CB) subunits modulate the immune system. Formyl peptide receptors (FPRs) and lipoxin A(4) (LXA(4)) are involved in CTX's effect on macrophages and neutrophils. Dendritic cells (DCs) are plasticity cells involved in the induction of adaptive immunity and tolerance maintenance. Therefore, we evaluated the effect of CTX, CA or CB on the maturation of DCs derived from murine bone marrow (BM). According to data, CTX and CB-but not CA-induced an increase of MHC-II, but not costimulatory molecules on DCs. Furthermore, CTX and CB inhibited the expression of costimulatory and MHC-II molecules, secretion of proinflammatory cytokines and NF-kappa Bp65 and p38/ERK1/2-MAPK signaling pathways by LPS-incubated DCs. Differently, CTX and CB induced IL-10, PGE(2) and LXA(4) secretion in LPS-incubated DCs. Lower proliferation and IL-2 secretion were verified in coculture of CD3(+) cells and DCs incubated with LPS plus CTX or CB compared with LPS-incubated DCs. The effect of CTX and CB on DCs was abolished in cultures incubated with a FPRs antagonist. Hence, CTX and CB exert a modulation on functional activity of DCs; we also checked the involvement the FPR family on cell activities. (AU)

• Processo FAPESP: 14/13085-7 - Mecanismos moleculares envolvidos na supressão da resposta imune aos helmintos: estudo da via de sinalização intracelular mediada pela interação de antígenos de Ascaris suum com DC-SIGN e MR em células dendríticas
• Beneficiário: Bruna Cristina Favoretto
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 10/10393-1 - Estudo da participação dos receptores DC-SIGN e MR nos mecanismos de supressão da resposta imune induzida por componentes de alta massa molecular do extrato de Ascaris suum
• Beneficiário: Bruna Cristina Favoretto
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/15608-0 - Estudo dos mecanismos moleculares envolvidos na imunomodulação exercida por antígenos de alta massa molecular de Ascaris suum, crotoxina e fosfolipase A2 do veneno de Crotalus durissus terrificus
• Beneficiário: Eliana Faquim de Lima Mauro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/23735-0 - Mecanismos envolvidos na modulação da resposta imune induzidos por antígenos de alta massa molecular do extrato de Ascaris suum e crotoxina isolada do veneno de Crotalus durissus terrificus
• Beneficiário: Eliana Faquim de Lima Mauro
• Modalidade de apoio: Auxílio à Pesquisa - Regular