S-Nitrosothiols Are Stored by Platelets and Released during PlateletNeutrophil Interactions
Authors: Hirayama A.; Noronha-Dutra A.A.; Gordge M.P.; Neild G.H.; Hothersall J.S.
Source: Nitric Oxide, Volume 3, Number 2, April 1999 , pp. 95-104(10)
Publisher: Academic Press
Abstract:
Interaction between platelets and neutrophils is important in vascular injury. We have investigated the storage and release of nitric oxide (NO) by platelets interacting with neutrophils. Shear-activated platelets were added to neutrophils in suspension and both superoxide and peroxynitrite formations monitored by lucigenin- and luminol-enhanced chemiluminescence. In addition, intraplatelet S-nitrosothiols were measured by dichlorofluorescein fluorescence following displacement of NO by mercuric chloride. Addition of activated platelets to neutrophils caused free radical production and plateletneutrophil rosette formation. Pretreatment of platelets with 20
M S-nitrosoglutathione changed the balance between luminol and lucigenin chemiluminescence in favor of luminol, whereas S-nitrosoglutathione in platelet-free plasma did not produce these changes. This pattern was also observed both following inhibition of neutrophil NO synthase and in a neutrophil-free superoxide-generating system. Inhibition of platelet NO synthase decreased luminol and increased lucigenin chemiluminescence. These effects were reversed by l-arginine. Platelet activation increased intraplatelet S-nitrosothiols from 1.93 ± 0.19 (mean ± SD) to 4.9 ± 1.10 × 10-18 mol/platelet (P < 0.01); this increase halved following NO synthase inhibition, but was enhanced by
220% following incubation with S-nitrosoglutathione. These results show that during shear stress platelets store S-nitrosothiols, which can be derived either endogenously from NO synthesis or exogenously by sequestration of S-nitrosoglutathione. Release of stored NO during plateletneutrophil interaction alters the interaction of NO with superoxide and could modulate vascular inflammation. Copyright 1999 Academic Press.
Language: English
Document Type: Research article
Affiliations: Department of Medicine, University College London, London, United Kingdom:

Click here for Page Help