Effects of jarastatin, a novel snake venom disintegrin, on neutrophil migration and actin cytoskeleton dynamics

A new disintegrin, an RGD-containing peptide of 6 kDa called jarastatin, wa s purified from Bothrops jararaca venom. It is a potent inhibitor of platel et aggregation induced by ADP, collagen, and thrombin. The effect of jarast atin on neutrophil migration in vivo and in vitro and on the actin cytoskel eton dynamics of these cells was investigated. Incubation in, vitro with ja rastatin significantly inhibited, in a concentration-dependent manner, the chemotaxis of human neutrophils toward fMLP, IL-8, and jarastatin itself. D espite this inhibitory effect, jarastatin induced neutrophil chemotaxis. A significant increase of F-actin content was observed in jarastatin-treated neutrophils, Furthermore, as demonstrated by confocal microscopy after FITC -phalloidin labeling, these cells accumulated F-actin at the plasmalemma, a distribution similar to that observed in fMLP-stimulated cells. Pretreatme nt of mice with jarastatin inhibited neutrophil migration into peritoneal c avities induced by carrageenan injection. The results suggest that binding of jarastatin to neutrophil integrins promotes cellular activation and trig gers a dynamic alteration of the actin filament system and that this is one of the first event in integrin-mediated signaling. (C) 1999 Academic Press .