Endothelial E- and P-selectin expression in iNOS- deficient mice exposed to polymicrobial sepsis.
In vitro, nitric oxide (NO) decreases leukocyte adhesion to endothelium by attenuating endothelial adhesion molecule expression. In vivo, lipopolysaccharide-induced leukocyte rolling and adhesion was greater in inducible NO synthase (iNOS)-/- mice than in wild-type mice. The objective of this study was to assess E- and P-selectin expression in the microvasculature of iNOS-/- and wild-type mice subjected to acute peritonitis by cecal ligation and perforation (CLP). E- and P-selectin expression were increased in various organs within the peritoneum of wild-type animals after CLP. This CLP-induced upregulation of E- and P-selectin was substantially reduced in iNOS-/- mice. Tissue myeloperoxidase (MPO) activity was increased to a greater extent in the gut of wild-type than in iNOS-/- mice subjected to CLP. In the lung, the reduced expression of E-selectin in iNOS-/- mice was not associated with a decrease in MPO. Our findings indicate that NO derived from iNOS plays an important role in sepsis-induced increase in selectin expression in the systemic and pulmonary circulation. However, in iNOS-/- mice, sepsis-induced leukocyte accumulation is affected in the gut but not in the lungs.
Lush
C W
CW
Department of Physiology, University of Western Ontario, London, Ontario, Canada N6A 5C1.
Cepinskas
G
G
Sibbald
W J
WJ
Kvietys
P R
PR
D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001424:Bacterial Infections / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000172:deficiency* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D019007:P-Selectin / Q000378:metabolism*; D010538:Peritonitis / Q000378:metabolism / Q000382:microbiology; D009195:Peroxidase / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D015854:Up-Regulation
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D019040:E-Selectin; C065289:ICAM2 protein, human; D019007:P-Selectin; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse