Modulation of Adhesion Molecule Expression in Pulmonary Vascular Endothelium by Oxygen

Abstract

Pulmonary oxygen toxicity (POT) is an important clinical problem that occurs in patients on long-term mechanical ventilation requiring a high inspired-oxygen concentration. Although the histological evidence of POT is pulmonary edema with neutrophil infiltration into the lung parenchyma, the pathogenesis of POT is not fully understood. To elucidate the mechanism of the development of POT, we investigated the effect of hyperoxia (90% O2, 5% CO2) on adhesion molecule expression in cultured human endothelial cells. The level of intercellular adhesion molecule-1 (ICAM-1) expression had increased in hyperoxia-exposed endothelial cells at 48h and at 72h as compared with normoxic control (21% O2, 5% CO2). In contrast, the levels of P-selectin and E-selectin expression were unchanged during hyperoxic exposure. These hyperoxia-induced ICAM-1 expressions were dose dependently attenuated by a protein kinase C inhibitor (H-7). The levels of ICAM-1 mRNA and the numbers of adherent neutrophils were increased at 48h and at 72 h of hyperoxia-exposed endothelial cells. These results suggest that increased ICAM-1 expression in endothelial cells plays an important role in neutrophil accumulation during POT.