Laboratório de Imunologia Celular Aplicada à Saúde, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho, RO, Brazil; Programa de Pós-Graduação em Biologia Experimental, PGBIOEXP, Núcleo de Saúde, NUSAU, Universidade Federal de Rondônia, UNIR, Porto Velho, RO, Brazil.
Programa de Pós-Graduação em Biologia Experimental, PGBIOEXP, Núcleo de Saúde, NUSAU, Universidade Federal de Rondônia, UNIR, Porto Velho, RO, Brazil; Centro de Estudos de Biomoléculas Aplicadas à Saúde (CEBio), Fundação Oswaldo Cruz, FIOCRUZ Rondônia e Departamento de Medicina, Universidade Federal de Rondônia, UNIR, Porto Velho, RO, Brazil; Centro de Pesquisa em Medicina Tropical (CEPEM), Porto Velho, RO, Brazil.
Int J Biol Macromol. 2017 Dec;105(Pt 1):1117-1125. doi: 10.1016/j.ijbiomac.2017.07.140. Epub 2017 Jul 23.
Crotalus Neutralizing Factor (CNF) is an inhibitor of phospholipase A (PLA), present in the blood plasma of Crotalus durissus terrificus snake. This inhibitor neutralizes the lethal and enzymatic activity of crotoxin, the main neurotoxin from this venom. In this study, we investigated the effects of CNF on the functionality of human peripheral blood mononuclear cells (PBMCs) and human neutrophils. The following parameters were evaluated: viability and proliferation, chemotaxis, cytokines and LTB production, cytosolic PLAs activity, myeloperoxidase (MPO) and superoxide anion (O) production. CNF showed no toxicity on PBMCs or neutrophils, and acts by stimulating the release of TNF-α and LTB, but neither stimulates IL-10 and IL-2 nor affects PBMCs proliferation and O release. In neutrophils, CNF induces chemotaxis but does not induce the release of both MPO and O. However, it induces LTB and IL-8 production. These data show the influence of CNF on PBMCs' function by inducing TNF-α and LTB production, and on neutrophils, by stimulating chemotaxis and LTB production, via cytosolic PLA activity, and IL-8 release. The inflammatory profile produced by CNF is shown for the first time. Our present results suggest that CNF has a role in activation of leukocytes and exert proinflammatory effects on these cell.
响尾蛇抗中性粒细胞因子（CNF）是一种存在于响尾蛇（Crotalus durissus terrificus）血浆中的磷脂酶 A（PLA）抑制剂。这种抑制剂能中和响尾蛇毒液中的主要神经毒素——响尾蛇神经毒素（crotoxin）的致死和酶活性。在这项研究中，我们研究了 CNF 对人外周血单个核细胞（PBMC）和人中性粒细胞功能的影响。评估了以下参数：细胞活力和增殖、趋化性、细胞因子和 LTB 产生、胞质 PLA 活性、髓过氧化物酶（MPO）和超氧阴离子（O）产生。CNF 对 PBMCs 或中性粒细胞均无毒性作用，通过刺激 TNF-α 和 LTB 的释放而发挥作用，但既不刺激 IL-10 和 IL-2 的产生，也不影响 PBMCs 的增殖和 O 的释放。在中性粒细胞中，CNF 诱导趋化性，但不诱导 MPO 和 O 的释放。然而，它诱导 LTB 和 IL-8 的产生。这些数据表明，CNF 通过诱导 TNF-α 和 LTB 的产生，对 PBMCs 的功能产生影响，通过刺激胞质 PLA 活性和 IL-8 的释放，对中性粒细胞产生趋化性和 LTB 的产生产生影响。首次显示了 CNF 对中性粒细胞功能的影响。我们目前的研究结果表明，CNF 在激活白细胞中起作用，并对这些细胞发挥促炎作用。
