Interaction of disintegrins with human neutrophils induces cytoskeleton reorganization, focal adhesion kinase activation, and extracellular‐regulated kinase‐2 nuclear translocation, interfering with the chemotactic function

ABSTRACT 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...

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Bibliographic Details
Published in:The FASEB journal 2001-07, Vol.15 (9), p.1643-1645
Main Authors: Coelho, Ana Lucia J., De Freitas, Marta S., Mariano-Oliveira, Andrea, Oliveira-Carvalho, Ana L., Zingali, Russolina B., Barja-Fidalgo, Christina
Format: Article
Language:English
Subjects:
actin cytoskeleton
Actins - physiology
Active Transport, Cell Nucleus - drug effects
chemotaxis
Chemotaxis - drug effects
Chemotaxis - physiology
Cytoskeleton - drug effects
Cytoskeleton - physiology
disintegrins
Disintegrins - pharmacology
Enzyme Activation - drug effects
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
Humans
In Vitro Techniques
Mitogen-Activated Protein Kinase 1 - metabolism
Mitogen-Activated Protein Kinases - metabolism
neutrophils
Neutrophils - drug effects
Neutrophils - enzymology
Neutrophils - metabolism
Neutrophils - physiology
Protein-Tyrosine Kinases - metabolism
Protein-Tyrosine Kinases - physiology
Signal Transduction
tyrosine kinase pathway
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Summary:ABSTRACT 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.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.00-0812fje