10362674

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6 Pt 2

Nitric oxide (NO) is known to be an important endogenous modulator of leukocyte-endothelial cell interactions within the microcirculation. We examined leukocyte rolling and adhesion under baseline conditions and following thrombin (0.25 U/ml) superfusion in the mesentery of wild-type, inducible NOS (iNOS)-deficient (-/-), neuronal NOS (nNOS) -/-, and endothelial cell NOS (ecNOS) -/- mice to further our understanding of NO and leukocyte function. Baseline leukocyte rolling (cells/min) was significantly elevated in both the nNOS -/- (30.0 +/- 4.0) and ecNOS -/- mice (67.0 +/- 12.0) compared with wild-type mice (11.0 +/- 1.4). In addition, baseline leukocyte adherence (cells/100 micrometers of vessel) was also significantly elevated in the nNOS -/- (5.2 +/- 1.0) and ecNOS -/- (13.0 +/- 1.3) compared with wild-type animals (1.3 +/- 0.5). Deficiency of iNOS had no effect on baseline leukocyte rolling or adhesion in the mesentery. Baseline surface expression of P-selectin was observed in 68.0 +/- 9.0% of intestinal venules in ecNOS -/- mice compared with 10.0 +/- 2.0% in wild-type mice. Additional studies demonstrated that administration of an anti-P-selectin monoclonal antibody (RB40. 34) or the soluble P-selectin ligand, PSGL-1, completely inhibited the increased rolling and firm adhesion response in nNOS -/- and ecNOS -/- mice. Transmigration of neutrophils into the peritoneum following thioglycollate injection was also significantly augmented in nNOS -/- and ecNOS -/- mice. These studies clearly indicate the NO derived from both nNOS and ecNOS is critical in the regulation of leukocyte-endothelial cell interactions.

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MEDLINE

0002-9513

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H1943-50

pubmed-meshheading:10362674-Animals, pubmed-meshheading:10362674-Antibodies, pubmed-meshheading:10362674-Blood Cell Count, pubmed-meshheading:10362674-Blood Vessels, pubmed-meshheading:10362674-Cell Adhesion, pubmed-meshheading:10362674-Endothelium, Vascular, pubmed-meshheading:10362674-Gene Targeting, pubmed-meshheading:10362674-Hemodynamics, pubmed-meshheading:10362674-Leukocytes, pubmed-meshheading:10362674-Mice, pubmed-meshheading:10362674-Neutrophils, pubmed-meshheading:10362674-Nitric Oxide Synthase, pubmed-meshheading:10362674-Nitric Oxide Synthase Type I, pubmed-meshheading:10362674-Nitric Oxide Synthase Type II, pubmed-meshheading:10362674-Nitric Oxide Synthase Type III, pubmed-meshheading:10362674-P-Selectin, pubmed-meshheading:10362674-Recombinant Proteins, pubmed-meshheading:10362674-Splanchnic Circulation, pubmed-meshheading:10362674-Thioglycolates, pubmed-meshheading:10362674-Thrombin

Leukocyte-endothelial cell interactions in nitric oxide synthase-deficient mice.

Journal Article, Research Support, U.S. Gov't, P.H.S.