Nitric oxide inhibits neutrophil adhesion to cytokine-activated cardiac myocytes.
Neutrophils play important roles in myocardial injury in which an inflammatory reaction ensues. We investigated the role of nitric oxide (NO) in neutrophil adhesion to cardiac myocytes. Isolated adult rat myocytes were coincubated with human neutrophils, and the number of neutrophils adherent to myocytes was microscopically counted. The adhesion increased up to 2.4-fold when both myocytes and neutrophils were activated by interleukin-1 beta (IL-1 beta) and platelet-activating factor (PAF), respectively. The NO donors, S-nitroso-N-acetylpenicillamine (SNAP) and sodium nitroprusside (SNP), inhibited the adhesion by 50% when administered to neutrophils before activation. However, when activated neutrophils were added to myocytes that had been incubated with NO donors during IL-1 beta stimulation, the inhibition of adhesion was not observed. Pretreatment of neutrophils with SNAP or 8-bromoguanosine 3',5'-cyclic monophosphate did not reduce PAF-induced CD11b/CD18 expression determined by flow cytometry, nor did simultaneous treatment of myocytes with IL-1 beta and SNAP decrease IL-1 beta-induced intercellular adhesion molecule-1 expression determined by immunofluorescence staining and enzyme-linked immunosorbent assay. Thus NO inhibits neutrophil-myocyte adhesion, mainly acting on neutrophils without quantitatively affecting the upregulation of CD11b/CD18.
Ohashi
Y
Y
First Department of Internal Medicine, Kobe University School of Medicine, Japan.
Kawashima
S
S
Hirata
K
K
Akita
H
H
Yokoyama
M
M
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015815:Cell Adhesion Molecules; D016207:Cytokines; D009569:Nitric Oxide