Nitric oxide reduces endothelial expression of intercellular adhesion molecule (ICAM)-1.
Nitric oxide (NO.) has proven effective in improving oxygenation and reducing pulmonary hypertension in the acute respiratory distress syndrome (ARDS), but the precise mechanism remains unclear. NO. has been shown to reduce leukocyte-endothelial adhesion, attenuate neutrophil (PMN) sequestration, and protect endothelium from an inflammatory insult. Intercellular adhesion molecule (ICAM)-1 is a pivotal regulator of PMN-endothelial adhesion and, thus, a critical mediator of PMN cytotoxicity. Consequently, we hypothesized that NO. suppresses ICAM-1 expression on endothelium. Human umbilical vein endothelial cells (HUVEC) were cultured. The NO. donor 3-morpholinosidnonimine (SIN-1) (0.1-10 microM) was incubated with HUVEC for 4 hr. In separate experiments, HUVEC were incubated with bacterial lipopolysaccharide (LPS) (100 ng/ml) alone or following SIN-1 pretreatment. ICAM-1 expression on HUVEC was measured by flow cytometric analysis. SIN-1 (1 and 10 microM) reduced the expression of ICAM-1 on resting HUVEC by 58 and 47%, respectively. LPS upregulated ICAM-1 expression; however, this was not affected by SIN-1 pretreatment. We conclude that NO. reduces constitutive endothelial expression of ICAM-1, but does not prevent LPS-stimulated upregulation of ICAM-1 expression. Downregulation of ICAM-1 may be a mechanism whereby NO. protects resting endothelium (distant organ bed) from circulating primed or activated PMNs, but may not be as effective at a primary inflammatory site.
Biffl
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WL
Department of Surgery, Denver General Hospital, University of Colorado Health Sciences Center 80204, USA.
Moore
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EE
Moore
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Barnett
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C
D000704:Analysis of Variance; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D014471:Umbilical Veins; D014665:Vasodilator Agents / Q000494:pharmacology*
D008070:Lipopolysaccharides; D014665:Vasodilator Agents; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine