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iNOS expression in human intestinal microvascular endothelial cells inhibits leukocyte adhesion
- Source :
- American Journal of Physiology-Gastrointestinal and Liver Physiology. 275:G592-G603
- Publication Year :
- 1998
- Publisher :
- American Physiological Society, 1998.
-
Abstract
- 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 substratel-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.
- Subjects :
- Lipopolysaccharides
Umbilical Veins
Nitric Oxide Synthase Type III
Endothelium
Physiology
Nitric Oxide Synthase Type II
Biology
Arginine
Polymerase Chain Reaction
Gene Expression Regulation, Enzymologic
Endothelial activation
Intestinal mucosa
Physiology (medical)
Cell Adhesion
Leukocytes
medicine
Humans
Enzyme Inhibitors
Intestinal Mucosa
Cell adhesion
Cells, Cultured
DNA Primers
omega-N-Methylarginine
Hepatology
Tumor Necrosis Factor-alpha
Cell adhesion molecule
Lysine
Microcirculation
Gastroenterology
Cell biology
Endothelial stem cell
Nitric oxide synthase
medicine.anatomical_structure
Immunology
biology.protein
Omega-N-Methylarginine
Endothelium, Vascular
Nitric Oxide Synthase
Subjects
Details
- ISSN :
- 15221547 and 01931857
- Volume :
- 275
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Accession number :
- edsair.doi.dedup.....7674835cfb56741bb39d029180b99e80