RESUMO
Crotoxin is the main neurotoxic component of Crotalus durissus terrificus snake venom and modulates immune and inflammatory responses, interfering with the activity of leukocytes. In the present work, the effects of crotoxin on the number of blood and lymphatic leukocytes and on lymph nodes and spleen lymphocytes population were investigated. The toxin s.c. administered to male Wistar rats, decreases the number of lymphocytes in blood and lymph circulation and increases the content of B and T-lymphocytes in lymph nodes. These effects were detected 1-2h after treatment. The crotoxin molecule is composed of two subunits, an acidic non-toxic polypeptide, named crotapotin and a toxic basic phospholipase A(2) (PLA(2)). PLA(2), but not crotapotin, decreased the number of circulating blood and lymph lymphocytes. Crotoxin promotes leukocyte adherence to endothelial cells of blood microcirculation and to lymph node high endothelial venules, which might contribute to the drop in the number of circulating lymphocytes. Crotoxin increases expression of the adhesion molecule LFA-1 in lymphocytes. The changes in the expression of the adhesion molecule might contribute, at least in part, for the increased leukocyte adhesion to endothelium. Zileuton, a 5-lipoxygenase inhibitor, blocked the decrease in the number of circulating leukocytes induced by crotoxin and also abolished the changes observed in leukocyte-endothelial interactions, suggesting the involvement of lipoxygenase-derived mediators in the effects of the toxin.
Assuntos
Moléculas de Adesão Celular/fisiologia , Crotoxina/farmacologia , Lipoxigenase/fisiologia , Linfócitos/efeitos dos fármacos , Animais , Adesão Celular/efeitos dos fármacos , Moléculas de Adesão Celular/metabolismo , Crotoxina/química , Eicosanoides/metabolismo , Eicosanoides/fisiologia , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Hidroxiureia/análogos & derivados , Hidroxiureia/farmacologia , Inibidores de Lipoxigenase/farmacologia , Linfa/citologia , Linfa/metabolismo , Linfonodos/citologia , Linfonodos/metabolismo , Vasos Linfáticos/citologia , Vasos Linfáticos/metabolismo , Contagem de Linfócitos , Linfócitos/sangue , Masculino , Fosfolipases A2/farmacologia , Ratos , Ratos Wistar , Baço/citologia , Baço/metabolismo , Ducto Torácico/citologia , Ducto Torácico/metabolismoRESUMO
The expulsion of antibody-damaged Nippostrongylus brasiliensis nematodes from the intestine of rats irradiated with 750 rad 60Co was induced by thoracic duct lymph (TDL) or mesenteric lymph node (MLN) cells apparently without the help of bone marrow-derived cells. The effector cells were present in the TDL or MLN of rats by the 8th day after infection and could be recovered from the peritoneal cavity. The ability of TDL cells to transfer immunity to irradiated recipients was undiminished when the cells with immunoglobulin on their surface were removed. These results suggest that, following antibody damage, this nematode is expelled by nonimmunoglobulin-bearing lymphocytes which are effective in the absence of newly formed cells derived from the cell recipients.