ABSTRACT
The Crotalus durissus terrificus rattlesnake venom, its main toxin, crotoxin (CTX), and its crotapotin (CA) and phospholipase A2 (CB) subunits modulate the immune system. Formyl peptide receptors (FPRs) and lipoxin A4 (LXA4) 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-κBp65 and p38/ERK1/2-MAPK signaling pathways by LPS-incubated DCs. Differently, CTX and CB induced IL-10, PGE2 and LXA4 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.
Subject(s)
Crotoxin/pharmacology , Dendritic Cells/drug effects , Dendritic Cells/metabolism , Immunomodulation/drug effects , Receptors, Formyl Peptide/metabolism , Animals , Cytokines/metabolism , Dendritic Cells/immunology , Gene Expression Regulation/drug effects , Histocompatibility Antigens Class II/genetics , Inflammation Mediators/metabolism , Lipopolysaccharides/immunology , Male , Mice , NF-kappa B/metabolism , Phosphorylation , Signal Transduction/drug effects , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Crotalus durissus terrificus venom and its main component, crotoxin (CTX), have the ability to down-modulate the immune system. Certain mechanisms mediated by cells and solublefactors of the immune system are responsible for the elimination of pathogenic molecules to ensure the specific protection against subsequent antigen contact. Accordingly, weevaluated the immunomodulatory effects of CTX on the immune response of mice that had been previously primed by immunisation with human serum albumin (HSA). CTX inoculationafter HSA immunisation, along with complete Freunds adjuvant (CFA) or Aluminium hydroxide (Alum) immunisation, was able to suppress anti-HSA IgG1 and IgG2a antibodyproduction. We showed that the inhibitory effects of this toxin are not mediated by necrosis or apoptosis of any lymphoid cell population. Lower proliferation of T lymphocytesfrom mice immunised with HSA/CFA or HSA/Alum that received the toxin wasobserved in comparison to the mice that were only immunised. In conclusion, CTX is able to exert potent inhibitory effects on humoural and cellular responses induced by HSAimmunisation, even when injected after an innate immune response has been initiated.
Subject(s)
Mice , Freund's Adjuvant/therapeutic use , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/therapeutic use , Crotoxin/antagonists & inhibitors , Crotoxin/immunology , Snake Venoms/analysis , Snake Venoms/immunology , Snake Venoms/therapeutic use , Immunity, Cellular , Immunity, Cellular/immunology , Immunity, HumoralABSTRACT
Crotalus durissus terrificus venom and its main component, crotoxin (CTX), have the ability to down-modulate the immune system. Certain mechanisms mediated by cells and soluble factors of the immune system are responsible for the elimination of pathogenic molecules to ensure the specific protection against subsequent antigen contact. Accordingly, we evaluated the immunomodulatory effects of CTX on the immune response of mice that had been previously primed by immunisation with human serum albumin (HSA). CTX inoculation after HSA immunisation, along with complete Freund's adjuvant (CFA) or Aluminium hydroxide (Alum) immunisation, was able to suppress anti-HSA IgG1 and IgG2a antibody production. We showed that the inhibitory effects of this toxin are not mediated by necrosis or apoptosis of any lymphoid cell population. Lower proliferation of T lymphocytes from mice immunised with HSA/CFA or HSA/Alum that received the toxin was observed in comparison to the mice that were only immunised. In conclusion, CTX is able to exert potent inhibitory effects on humoral and cellular responses induced by HSA immunisation, even when injected after an innate immune response has been initiated.
