NITRIC-OXIDE REDUCES ENDOTHELIAL EXPRESSION OF INTERCELLULAR-ADHESIONMOLECULE (ICAM)-1

Nitric oxide (NO.) has proven effective in improving oxygenation and r educing pulmonary hypertension in the acute respiratory distress syndr ome (ARDS), but the precise mechanism remains unclear. NO. has been sh own to reduce leukocyte-endothelial adhesion, attenuate neutrophil (PM N) sequestration, and protect endothelium from an inflammatory insult. Intercellular adhesion molecule (ICAM)-1 is a pivotal regulator of PM N-endothelial adhesion and, thus, a critical mediator of PMN cytotoxic ity. Consequently, we hypothesized that NO. suppresses ICAM-1 expressi on on endothelium. Human umbilical vein endothelial cells (HUVEC) were cultured. The NO. donor 3-morpholinosidnonimine (SIN-1) (0.1-10 mu M) was incubated with HUVEC for 4 hr. In separate experiments, HUVEC wer e incubated with bacterial lipopolysaccharide (LPS) (100 ng/ml) alone or following SIN-1 pretreatment. ICAM-1 expression on HUVEC was measur ed by flow cytometric analysis. SIN-1 (1 and 10 mu M) reduced the expr ession of ICAM-1 on resting HUVEC by 58 and 47%, respectively. LPS upr egulated ICAM-1 expression; however, this was not affected by SIN-1 pr etreatment. We conclude that NO. reduces constitutive endothelial expr ession 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 in flammatory site. (C) 1996 Academic Press, Inc.