Increases in oxygen tension stimulate expression of ICAM-1 and VCAM-1 on human endothelial cells

Increases in oxygen tension stimulate expression of ICAM-1 and VCAM-1 on hu man endothelial cells. Am. J. Physiol. 276 (Heart Circ. Physiol. 45): H2044 -H2052, 1999.-Leukocyte infiltration plays a major role in ischemia-associa ted organ dysfunction and damage. A crucial step for extravasation of white blood cells is binding of leukocyte beta-integrins to endothelial adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). To test for direct effects of oxygen on this process we studied ICAM-1 and VCAM-1 expression in human dermal microvascular and u mbilical vein endothelial cells (EC) exposed to different oxygen tensions i n the absence or presence of tumor necrosis factor-alpha (TNF-alpha). Hypox ia (95% N-2-5% CO2) resulted in a downregulation of basal but not TNF-alpha -induced expression of ICAM-1 and VCAM-1. Subsequent rises in oxygen (21, 4 0, or 95% O-2) led to marked increase of ICAM-1 and VCAM-1 cell surface and mRNA expression in both EC types, which after 16 h amounted to about one-t hird to one-half of maximal TNF-oc-induced expression. This increase was gr eatest after 0.5-h hypoxia and was blunted with prolonged hypoxic preincuba tion. Exposure of cells preincubated under "normoxic" (21% O-2) conditions to hyperoxia (40 or 95% O-2) also enhanced expression of both adhesion mole cules, but the increase was lower than in cells preexposed to hypoxia. The nitric oxide synthesis inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) enhanced ICAM-1 and VCAM-1 expression under basal and hypoxic conditions, but in the presence of L-NAME, levels in reoxygenated cells were not higher than basal levels. Moreover, the oxygen-induced rise could be mimicked by addition of H2O2 to normoxic cells, and the oxygen-induced expression of VC AM-1 but not of ICAM-1 was inhibited by addition of the free radical scaven gers superoxide dismutase, N-acetyl-L-cysteine, and pyrrolidinedithiocarbam ate. These data indicate that an increase in oxygen availability stimulates ICAM-1 and VCAM-1 expression on micro- and macrovascular EC, which may con tribute to adhesion and transmigration of different leukocyte populations i n ischemia-reperfusion injuries.