Laboratório de Bioquímica e Biotecnologia e Laboratório de Cultivo Celular e Anticorpos Monoclonais, Instituto de Pesquisas em Patologias Tropicais, Porto Velho, Rondônia, CEP 76812-245, Brazil.
Biochemistry (Mosc). 2013 Feb;78(2):194-203. doi: 10.1134/S0006297913020089.
The in vitro effects of BaltTX-I, a catalytically inactive Lys49 variant of phospholipase A2 (PLA2), and BaltTX-II, an Asp49 catalytically active PLA2 isolated from Bothrops alternatus snake venom, on thioglycollate-elicited macrophages (TG-macrophages) were investigated. At non-cytotoxic concentrations, the secretory PLA2 BaltTX-I but not BaltTX-II stimulated complement receptor-mediated phagocytosis. Pharmacological treatment of TG-macrophages with staurosporine, a protein kinase C (PKC) inhibitor, showed that this kinase is involved in the increase of serum-opsonized zymosan phagocytosis induced by BaltTX-I but not BaltTX-II secretory PLA2, suggesting that PKC may be involved in the stimulatory effect of this toxin in serum-opsonized zymosan phagocytosis. Moreover, BaltTX-I and -II induced superoxide production by TG-macrophages. This superoxide production stimulated by both PLA2s was abolished after treatment of cells with staurosporine, indicating that PKC is an important signaling pathway for the production of this radical. Our experiments showed that, at non-cytotoxic concentrations, BaltTX-I may upregulate phagocytosis via complement receptors, and that both toxins upregulated the respiratory burst in TG-macrophages.
研究了来自巴西矛头蝮蛇毒液的催化失活 Lys49 变体磷脂酶 A2（PLA2）BaltTX-I 和催化活性 Asp49 PLA2 BaltTX-II 在硫代乙醇酸盐诱导的巨噬细胞（TG-巨噬细胞）中的体外作用。在非细胞毒性浓度下，分泌型 PLA2 BaltTX-I 但不是 BaltTX-II 刺激补体受体介导的吞噬作用。用蛋白激酶 C（PKC）抑制剂 staurosporine 对 TG-巨噬细胞进行药理学处理表明，这种激酶参与了 BaltTX-I 但不参与 BaltTX-II 分泌型 PLA2 诱导的血清调理酵母聚糖吞噬作用的增加，表明 PKC 可能参与了该毒素在血清调理酵母聚糖吞噬作用中的刺激作用。此外，BaltTX-I 和 -II 诱导 TG-巨噬细胞产生超氧化物。这两种 PLA2 刺激的超氧化物产生在用 staurosporine 处理细胞后被消除，表明 PKC 是产生这种自由基的重要信号通路。我们的实验表明，在非细胞毒性浓度下，BaltTX-I 可能通过补体受体上调吞噬作用，并且两种毒素均上调 TG-巨噬细胞的呼吸爆发。
