Fernandes Cristina Maria, Zamuner Stella Regina, Zuliani Juliana Pavan, Rucavado Alexandra, Gutiérrez José Maria, Teixeira Catarina de Fátima Pereira
Laboratório de Farmacologia, Instituto Butantan, Ave Vital Brazil, 1500-05503 900 Sao Paulo, Brazil.
Toxicon. 2006 Apr;47(5):549-59. doi: 10.1016/j.toxicon.2006.01.009. Epub 2006 Mar 10.
The inflammatory events induced by BaP1, a 22.7 kDa metalloproteinase isolated from Bothrops asper snake venom, were studied. BaP1 i.p. injection in mice induced a marked inflammatory cell infiltrate into peritoneal cavity of animals with predominance of neutrophils in the early phase followed by mononuclear cells in the late period. Inhibition of enzymatic activity of BaP1 by chelation with EDTA resulted in a drastic reduction of this effect. In addition, BaP1 induced a significant increase of blood neutrophil numbers before its accumulation in peritoneal cavity, thus suggesting a stimulatory action of BaP1 on mechanisms of cell mobilization from bone marrow reserve compartments. A reduction in the number of neutrophils was observed in the exudate when antibodies against LECAM-1, CD18 and LFA-1 were used, suggesting the involvement of these adhesion molecules in the effects of BaP1. In contrast, there was no effect with antibodies against ICAM-1 and PECAM-1. Moreover, a conspicuous increment in the levels of IL-1 and TNF-alpha, but not of LTB4, was observed in peritoneal washes collected from mice injected with BaP1. It is concluded that BaP1 induces in vivo a marked leukocyte influx, which parallels an increased number of these cells in the blood, and is associated to the expression of specific leukocyte adhesion molecules and release of chemotactic inflammatory cytokines. Since BaP1 is a P-I class metalloproteinase, these results indicate that the proteolytic domain of metalloproteinases per se can trigger specific inflammatory events.
对从矛头蝮蛇毒中分离出的一种22.7 kDa金属蛋白酶BaP1所诱导的炎症事件进行了研究。给小鼠腹腔注射BaP1会诱导明显的炎症细胞浸润到动物的腹腔中，早期以中性粒细胞为主，后期则以单核细胞为主。通过与EDTA螯合抑制BaP1的酶活性会导致这种效应大幅降低。此外，BaP1在其在腹腔中积聚之前会导致血液中性粒细胞数量显著增加，这表明BaP1对骨髓储备区室的细胞动员机制具有刺激作用。当使用抗LECAM-1、CD18和LFA-1的抗体时，渗出液中的中性粒细胞数量减少，这表明这些黏附分子参与了BaP1的效应。相比之下，抗ICAM-1和PECAM-1的抗体则没有效果。此外，在注射了BaP1的小鼠的腹腔灌洗液中观察到IL-1和TNF-α水平显著升高，但LTB4水平没有升高。结论是，BaP1在体内诱导明显的白细胞流入，这与血液中这些细胞数量的增加平行，并且与特定白细胞黏附分子的表达和趋化性炎症细胞因子的释放有关。由于BaP1是一种P-I类金属蛋白酶，这些结果表明金属蛋白酶的蛋白水解结构域本身可以引发特定的炎症事件。
