Effects of Jarastatin, a Novel Snake Venom Disintegrin, on Neutrophil Migration and Actin Cytoskeleton Dynamics
Autor: | Ana Lucia J. Coelho, Ana Lucia Oliveira-Carvalho, Christina Barja-Fidalgo, Russolina B. Zingali, Marta S. De Freitas, Vivaldo Moura-Neto |
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Rok vydání: | 1999 |
Předmět: |
Integrins
Neutrophils Disintegrins Molecular Sequence Data Integrin Biology Mice Thrombin In vivo Crotalid Venoms medicine Disintegrin Animals Humans Bothrops Amino Acid Sequence Peritoneal Cavity Cytoskeleton Actin Sequence Homology Amino Acid Cell Membrane Interleukin-8 Chemotaxis Cell Biology Actin cytoskeleton Actins In vitro Cell biology Mice Inbred C57BL N-Formylmethionine Leucyl-Phenylalanine Chemotaxis Leukocyte biology.protein Oligopeptides Sequence Analysis Protein Binding medicine.drug |
Zdroj: | Experimental Cell Research. 251:379-387 |
ISSN: | 0014-4827 |
DOI: | 10.1006/excr.1999.4583 |
Popis: | A new disintegrin, an RGD-containing peptide of 6 kDa called jarastatin, was purified from Bothrops jararaca venom. It is a potent inhibitor of platelet aggregation induced by ADP, collagen, and thrombin. The effect of jarastatin on neutrophil migration in vivo and in vitro and on the actin cytoskeleton dynamics of these cells was investigated. Incubation in vitro with jarastatin significantly inhibited, in a concentration-dependent manner, the chemotaxis of human neutrophils toward fMLP, IL-8, and jarastatin itself. Despite 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. Pretreatment of mice with jarastatin inhibited neutrophil migration into peritoneal cavities induced by carrageenan injection. The results suggest that binding of jarastatin to neutrophil integrins promotes cellular activation and triggers a dynamic alteration of the actin filament system and that this is one of the first event in integrin-mediated signaling. |
Databáze: | OpenAIRE |
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