Farsky S H, Walber J, Costa-Cruz M, Cury Y, Teixeira C F
Laboratory of Pathophysiology, Institut Butantan, São Paulo, Brazil.
Toxicon. 1997 Feb;35(2):185-93. doi: 10.1016/s0041-0101(96)00135-3.
The effect of Bothrops jararaca crude venom (BjV) on the cellular component of inflammatory responses was investigated in vivo and in vitro. In vivo leukocyte accumulation and release of eicosanoids (thromboxane A2, TXA2, and leukotriene B4, LTB4) at the site of injection of the venom were assessed using the air pouch method in rats. Administration of BjV caused a significant cell accumulation, maximal values being obtained after 6-8 hr. Neutrophils were the predominant cell type in the inflammatory exudate. High concentrations of LTB4 were detected 1-4 hr after the injection of the venom. TXA2 concentrations were significantly increased only at the early stages of the response to the venom. In vitro chemotaxis assays were performed and showed that the venom per se was not able to induce oriented neutrophil migration because varying concentrations of the venom dissolved in Hanks' balanced salt solution (HBSS) evoked a response equivalent to that of HBSS alone. Furthermore, the venom did not affect cellular intrinsic mechanisms involved with neutrophil locomotion because previous incubation of the cells with BjV produced no effect. However, high concentrations of the venom were able to generate serum chemotactic factor(s). Incubation of serum with the venom evoked a neutrophil migration similar to that observed with serum activated by lipopolysaccharide from Escherichia coli. Participation of chemotactic factors derived from the complement system is suggested by data showing loss of this activity when serum was heated (56 degrees C) before the addition of BjV. The present results suggest that leukocyte accumulation in the locality of a lesion induced by BjV is dependent on secretion or activation of endogenous components responsible for several steps in leukocyte recruitment instead of a direct effect of the venom on leukocytes.
研究了巴西矛头蝮粗毒（BjV）对炎症反应细胞成分的体内和体外作用。在大鼠中采用气袋法评估了体内毒液注射部位的白细胞积聚以及类花生酸（血栓素A2、TXA2和白三烯B4、LTB4）的释放。注射BjV后导致显著的细胞积聚，在6 - 8小时后达到最大值。中性粒细胞是炎性渗出物中的主要细胞类型。注射毒液后1 - 4小时检测到高浓度的LTB4。仅在对毒液反应的早期阶段，TXA2浓度显著升高。进行了体外趋化性分析，结果表明毒液本身不能诱导定向的中性粒细胞迁移，因为溶解在汉克斯平衡盐溶液（HBSS）中的不同浓度毒液引发的反应与单独的HBSS相当。此外，毒液不影响与中性粒细胞运动相关的细胞内在机制，因为预先用BjV孵育细胞没有产生影响。然而，高浓度的毒液能够产生血清趋化因子。毒液与血清孵育引发的中性粒细胞迁移类似于用大肠杆菌脂多糖激活的血清所观察到的迁移。数据显示，血清在加入BjV之前加热（56摄氏度）会导致这种活性丧失，这表明补体系统衍生的趋化因子参与其中。目前的结果表明，BjV诱导的病变部位白细胞积聚依赖于负责白细胞募集多个步骤的内源性成分的分泌或激活，而不是毒液对白细胞的直接作用。
