pH dependence of neutrophil-endothelial cell adhesion and adhesion molecule expression

Neutrophil adhesion to the vascular endothelium is enhanced during tissue ischemia and/or inflammation, conditions that are associated with tissue acidosis. This study examined the effects of hypercarbic acidosis (10 or 20% CO₂) and of hypocarbic alkalosis (0% CO₂) on human neutrophil CD18 and human aortic endothelial cell intercellular adhesion molecule-1 (ICAM-1) vascular cell adhesion molucule-1 (VCAM-1), and E-selectin expression quantified by flow cytometry. Acidosis with 20% CO₂ for 4 h decreased ICAM- 1 to 60.6 ± 9.7% of control. In contrast, alkalosis with 0% CO₂ for 4 h enhanced ICAM-1 expression to 143.8 ± 10.1% of control. There was no pH dependence of VCAM-1 or E-selectin expression. Tumor necrosis factor-α (TNF- α; 10 ng/ml) increased endothelial ICAM-1, E-selectin, and VCAM-1; under these conditions, acidosis with 20% CO₂ blunted both ICAM-1 and E-selectin surface expression compared with 5% CO₂-, TNF-α-treated cells. Hypercarbic acidosis with 20% CO₂ increased neutrophil CD18 expression and enhanced neutrophil adhesion. This latter effect was inhibited by neutrophil pretreatment with an anti-CD18 monoclonal antibody. In contrast, when only endothelial cells were preincubated with the hypercarbic buffer, neutrophil adhesion diminished to 55.6 ± 7.84% of control. The results suggest that acidosis generated during tissue ischemia/inflammation may induce CDl8- mediated neutrophil adhesion despite a decrease in ICAM-1 expression.