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

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.

Infecção das brânquias de tilápia do Nilo (Oreochromis niloticus) por Myxosporea / Infection of the gills of Nile tilapia (Oreochromis niloticus) by Myxosporea

Neste estudo, 85 tilápias do Nilo (Oreochromis niloticus Linnaeus, 1758) foram coletadas em um lago de pesca recreativa (n = 35) e no lago do parque do Ibirapuera (n = 50), ambos localizados na cidade de São Paulo. Após a eutanásia, as brânquias dos peixes foram examinadas a fresco e por técnicas histológicas para identificar mixosporídeos. Foram observados mixosporídeos somente nos peixes capturados no lago de pesca recreativa com prevalência de 45,7% (16/35). Os esporos de Henneguya sp. foram encontrados em esfregaços a fresco (11,4%, 4/35). A prevalência de Myxobolus sp. foi de 34,3% (12/35), sendo os plasmódios deste gênero identificados de acordo com a localização nas brânquias, no epitélio (75%, 9/12), nos vasos sanguíneos (16,2%, 2/12), e na musculatura branquial (0,8%, 1/12). A presença de mixosporídeos estava relacionada com hiperplasia epitelial, fusão das lamelas, hiperplasia de células mucosas, reação inflamatória e outras alterações patológicas. Assim conclui-se que as prevalências de Myxobolus sp. e Henneguya sp. nas brânquias de O. niloticus foram altas e estavam associadas à lesões histopatológicas significantes, o que evidencia a importância desses cnidários patogênicos para as culturas peixes.(AU)

In this study, 85 Nile tilapia (Oreochromis niloticus Linnaeus, 1758) were collected in recreational fishing lake (n=35) and Lake Ibirapuera Park (n=50), both located in the city of São Paulo. After euthanasia, the fish gills were examined fresh and after histological techniques for the presence of myxosporea. Myxosporeans were observed only in recreational fishing lake with a prevalence of 45.7% (16/35). Henneguya sp. (11.4%, 4/35) and Myxobolus sp. (34.3%, 12/35) were myxosporeans observed in this study. Spores of Henneguya sp. were found in smears fresh gills. The plasmodium of Myxobolus found was of the types epithelial (75%, 9/12), vascular (16.2%, 2/12), and muscle, muscle located in the gills (0.8%; 1/12). The presence of myxosporea was related to epithelial hyperplasia, fusion of lamellae, hyperplasia of mucous cells, inflammation and other pathological changes. Thus it is concluded that prevalence of Myxobolus sp. and Henneguya sp. in gills of O. niloticus was high and was associated with significant histopathological lesions, which highlights the importance of these protozoa to fish cultures.(AU)

Crotoxin alters lymphocyte distribution in rats: Involvement of adhesion molecules and lipoxygenase-derived mediators.

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.