9724273

pubmed:Citation

3 Pt 1

Increased nitric oxide (NO) production by inducible nitric oxide synthase (iNOS) has been associated with intestinal inflammation, including human inflammatory bowel disease. However, NO can downregulate endothelial activation and leukocyte adhesion, critical steps in the inflammatory response. Using primary cultures of human intestinal microvascular endothelial cells (HIMEC), we determined the role of NO in the regulation of HIMEC activation and interaction with leukocytes. Both nonselective (NG-monomethyl-L-arginine) and specific (N-iminoethyl-L-lysine) competitive inhibitors of iNOS significantly increased binding of leukocytes by HIMEC activated with cytokines and lipopolysaccharide. Increased adhesion was reversible with the NOS substrate L-arginine and was not observed in human umbilical vein endothelial cells (HUVEC). Activation of HIMEC significantly upregulated HIMEC iNOS expression and NO production. NOS inhibitors did not augment cell adhesion molecule levels in activated HIMEC but did result in sustained increases in intracellular reactive oxygen species. In addition, antioxidant compounds reversed the effect of NOS inhibitors on HIMEC-leukocyte interaction. Taken together, these data suggest that after HIMEC activation, iNOS-derived NO is an endogenous antioxidant, downregulating leukocyte binding and potentially downregulating intestinal inflammation.

eng

IM

MEDLINE

0002-9513

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NLM

G592-603

pubmed-meshheading:9724273-Arginine, pubmed-meshheading:9724273-Cell Adhesion, pubmed-meshheading:9724273-Cells, Cultured, pubmed-meshheading:9724273-DNA Primers, pubmed-meshheading:9724273-Endothelium, Vascular, pubmed-meshheading:9724273-Enzyme Inhibitors, pubmed-meshheading:9724273-Gene Expression Regulation, Enzymologic, pubmed-meshheading:9724273-Humans, pubmed-meshheading:9724273-Intestinal Mucosa, pubmed-meshheading:9724273-Leukocytes, pubmed-meshheading:9724273-Lipopolysaccharides, pubmed-meshheading:9724273-Lysine, pubmed-meshheading:9724273-Microcirculation, pubmed-meshheading:9724273-Nitric Oxide Synthase, pubmed-meshheading:9724273-Nitric Oxide Synthase Type II, pubmed-meshheading:9724273-Nitric Oxide Synthase Type III, pubmed-meshheading:9724273-Polymerase Chain Reaction, pubmed-meshheading:9724273-Tumor Necrosis Factor-alpha, pubmed-meshheading:9724273-Umbilical Veins, pubmed-meshheading:9724273-omega-N-Methylarginine

iNOS expression in human intestinal microvascular endothelial cells inhibits leukocyte adhesion.

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