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Effects of nitric oxide and peroxynitrite on endotoxin‐induced leukocyte adhesion to endothelium
Author(s) -
Lelamali Kumtorn,
Wang Wei,
Gengaro Patricia,
Edelstein Charles,
Schrier Robert W.
Publication year - 2001
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1128
Subject(s) - peroxynitrite , nitric oxide , lipopolysaccharide , endothelium , adhesion , chemistry , nitric oxide synthase , cell adhesion , peroxynitrous acid , inflammation , endothelial stem cell , sepsis , immunology , biochemistry , in vitro , biology , superoxide , enzyme , endocrinology , organic chemistry
Leukocyte accumulation has been shown to be increased in sepsis. Moreover, in inducible nitric oxide synthase (iNOS) knockout mice, a further increase in leukocyte accumulation has been observed during sepsis, suggesting that nitric oxide (NO) may affect leukocyte/endothelial interaction. Accelerated peroxynitrite formation also occurs during sepsis. In the present study, the effect of peroxynitrite or NO on leukocyte adhesion to nitric oxide synthase (NOS)‐inhibited or endotoxin‐treated endothelium was examined. Bovine aortic endothelial cells were treated with either l ‐NAME or lipopolysaccharide (LPS) and interferon‐gamma for 4 hr and subsequent leukocyte adhesion was measured. Both l ‐NAME and LPS treatment resulted in increased leukocyte adhesion compared with control. Neither a peroxynitrite donor, SIN‐1, nor a direct NO donor, DETA‐NO, had any effect on leukocyte adhesion to untreated endothelium. However, when the l ‐NAME or LPS‐treated endothelial cells were treated simultaneously with either SIN‐1 or DETA‐NO, there was a significant reduction in leukocyte adhesion. Moreover, at the concentrations used in the present study, neither peroxynitrite nor NO showed harmful effects on normal cultured endothelial cells. These data demonstrating inhibition of leukocyte adhesion to endotoxin‐treated endothelium suggest that peroxynitrite or NO may exert a beneficial effect during sepsis. © 2001 Wiley‐Liss, Inc.