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-LXA4. These results indicate that
formyl peptide receptors mediate CTX-induced redistribution of
lymphocytes and that 15-epi-LXA4 is a key mediator of the immunosuppressive effects of CTX.