Keith Wilson
Faculty Member
Last active: 8/13/2019

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

Binion DG, Fu S, Ramanujam KS, Chai YC, Dweik RA, Drazba JA, Wade JG, Ziats NP, Erzurum SC, Wilson KT
Am J Physiol. 1998 275 (3): G592-603

PMID: 9724273 · DOI:10.1152/ajpgi.1998.275.3.G592

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.

MeSH Terms (20)

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

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