Journal
FASEB JOURNAL
Volume 15, Issue 7, Pages 1643-+Publisher
WILEY
DOI: 10.1096/fj.00-0812fje
Keywords
disintegrins; neutrophils; chemotaxis; tyrosine kinase pathway; actin cytoskeleton
Categories
Ask authors/readers for more resources
We previously demonstrated that jarastatin (JT), a new disintegrin from Bothrops jararaca venom, altered actin dynamics in human polymorphonuclear neutrophils (PMNs) and inhibited cell migration in vivo and in vitro (14). In this study, we evaluated the effects of JT and two other monomeric disintegrins, kistrin (KR) and flavoridin (FL), on PMN chemotaxis and chemokinesis in vitro and on the activation of integrin-mediated pathways. Although JT, but not KR or FL, was chemotactic, only KR was chemokinetic to PMN. However, preincubation of PMN with any disintegrins inhibited chemotaxis for fMLP. Treatment of PMN with JT and KR increased actin polymerization, whereas FL reduced the content of F-actin. The effects of JT and KR on actin dynamics were inhibited (50%) by genistein, a tyrosine kinase inhibitor. Accordingly, JT and KR induced an increase in tyrosine phosphorylation, whereas FL had no effect. The three disintegrins were able to induce focal adhesion kinase activation. However, JT and KR promoted Erk-2 nuclear translocation, and FL inhibited Erk-2 activation. The data suggest that although the disintegrins JT and KR directly activate integrin-coupled signaling, FL may interact differently with integrins, triggering an inhibitory pathway modulated by focal adhesion kinase activation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available