Nitric oxide modulates endotoxin-induced platelet-endothelial cell adhesion in intestinal venules


Cerwinka, Wolfgang H., Cooper, Dianne, Krieglstein, Christian F., Feelisch, Martin and Granger, D. Neil (2002) Nitric oxide modulates endotoxin-induced platelet-endothelial cell adhesion in intestinal venules. American Journal of Physiology. Heart and Circulatory Physiology, 282, (3), H1111-H1117. (doi:10.1152/ajpheart.00391.2001). (PMID:11834510).

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Description/Abstract

Although platelets have been implicated in the pathogenesis of vascular diseases, little is known about factors that regulate interactions between platelets and the vessel wall under physiological conditions. The objectives of this study were to 1) define the contribution of nitric oxide (NO) to endotoxin (lipopolysaccharide, LPS)-induced platelet-endothelial cell (P/E) adhesion in murine intestinal venules and 2) determine whether the antiadhesive action of NO is mediated by soluble guanylate cyclase (sGC). Adhesive interactions between platelets and endothelial cells were monitored by intravital microscopy. LPS administration into control wild-type mice (WT) resulted in a >15-fold increase in P/E adhesion. Similar responses were observed using endothelial NO synthase (eNOS)-deficient platelets. However, treatment with the NO donor diethylenetriamine-nitric oxide (DETA-NO) attenuated the P/E adhesion response to LPS, whereas the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester or eNOS deficiency resulted in an exacerbation. P/E adhesion response did not differ between LPS-treated WT and inducible NOS-deficient mice. Inhibition of sGC abolished the attenuating effects of DETA-NO, whereas the sGC activator 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) reduced LPS-induced P/E adhesion. These findings indicate that 1) eNOS-derived NO attenuates endotoxin-induced P/E adhesion and 2) sGC is responsible for the antiadhesive action of NO.

Item Type: Article
ISSNs: 0363-6135 (print)
1522-1539 (electronic)
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Keywords: endotoxemia, nitric oxide synthase, soluble guanylate cyclase, postcapillary venules
Subjects: Q Science > QP Physiology
Q Science > QR Microbiology > QR180 Immunology
Divisions: Faculty of Medicine > Infection, Inflammation and Immunity
ePrint ID: 337867
Date Deposited: 22 Jun 2012 13:25
Last Modified: 27 Mar 2014 20:21
URI: http://eprints.soton.ac.uk/id/eprint/337867

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