HYPOXIA-INDUCED ALTERATIONS OF NEUTROPHIL MEMBRANE-RECEPTORS

Extravasation of leukocytes at sites of ischemia may mediate tissue in jury. To determine how leukocyte accumulation may be induced by ischem ia, effects of hypoxia on basal neutrophil expression of adhesion and activation receptors were examined. Effects of hypoxia upon preactivat ed cells were also studied. To determine whether regulation of express ion is dependent on oxygen availability or on mitochondrial respiratio n, the effects of physical hypoxia (substitution of O-2 by nitrogen) w ere compared with those of chemical hypoxia with sodium cyanide (NaCN) . Leukocytes in whole blood (eight volunteers) were exposed either to hypoxia alone or to priming concentrations of lipopolysaccharide (LPS, 1 mu g/ml) followed by chemical hypoxia (NaCN, 1 mM) or physical hypo xia (PO2 of 1-10 torr) for various time intervals. Room air was contro lled and hypoxic cells were labeled with fluorescent monoclonal antibo dies to integrins CD18 and CD11b or to the 55-kDa TNF alpha cell surfa ce receptor (TNFR). Receptor concentrations were measured by flow cyto metry. Data were analyzed by ANOVA/Student's t test. Physical hypoxia increased expression of both CD11b and CD18 over time and augmented th eir LPS-induced up-regulation. Isolated chemical hypoxia did not chang e neutrophil expression of CD11b or CD18, but partially inhibited neut rophil CD11b and CD18 up-regulation by LPS. LPS-induced TNFR down-regu lation was not affected by physical hypoxia, which failed to alter TNF R expression in this model. Chemical hypoxia led to an up-regulation o f TNFR in neutrophils, which was opposed by LPS. Physical hypoxia exer ts a specific effect on expression of leukocyte receptors, which is su bstantially different from that exerted by chemical hypoxia. (C) 1995 Academic Press, Inc.