Rhodostomin, a disintegrin, inhibits adhesion of neutrophils to fibrinogen and attenuates superoxide production
Journal
Journal of Biomedical Science
Journal Volume
11
Journal Issue
5
Pages
683-691
Date Issued
2004
Author(s)
Abstract
Disintegrins are a group of Arg (or Lys)-Gly-Asp-containing snake venom proteins which inhibit platelet aggregation via the blockade of αIIbβ3 integrin. Here, we studied the effect of rhodostomin, a disintegrin purified from the venom of Calloselasma rhodostoma, on the functions of neutrophils. By flow cytometric analysis of whole blood, we found that rhodostomin interacted with leukocytes of the myeloid and monocytic lineage as well as with platelets. The binding of rhodostomin to neutrophils could reach saturation in a dose-dependent manner, and its binding was increased in neutrophils stimulated with phorbol 12-myristate 13-acetate (PMA) and N-formyl-Met-Leu-Phe. EDTA did not inhibit the binding of rhodostomin. In addition, bound rhodostomin was not internalized. Soluble fibrinogen, a natural ligand of Mac-1 (CD11b/CD18, αMβ2), and the peptide, GRGDS, inhibited the binding of rhodostomin to PMA-activated neutrophils, while 7E3, a monoclonal antibody (mAb) raised against β3 integrin, or mAbs raised against αM and β2 integrin did not. Rhodostomin blocked the Mac-1-dependent adhesion of neutrophils to immobilized fibrinogen, in parallel with decreasing the production of superoxide from adherent neutrophils. Taken together, our results indicate that rhodostomin binds to activated neutrophils in an RGD-dependent manner, blocks the adhesion of activated neutrophils to fibrinogen and attenuates superoxide production, suggesting that rhodostomin may have anti-inflammatory properties. Copyright © 2004 National Science Council, ROC and S. Karger AG, Basel.
Type
journal article