Activation of oxidative and arachidonic acid metabolism in neutrophils by respiratory syncytial virus antibody complexes: Possible role in disease

The effect of respiratory syncytial virus (RSV) antibody complexes on the metabolism of human neutrophils was determined by examining the generation of luminol-dependent chemiluminescence, superoxide, and thromboxane B₂. Incubation of neutrophils with RSV antibody complexes resulted in a significant increase in the production of chemiluminescence. The increase in chemiluminescence appeared to be due to (1) active phagocytosis of RSV antibody complexes as evidenced by 70% inhibition with cytochalasin B (P < 0.001) or (2) increased superoxide production as evidenced by 40% inhibition with superoxide dismutase (P < 0.001). The generation of superoxide was confirmed by specific analysis in a superoxide dismutase-inhibitable ferricytochrome c reduction assay. Of particular importance was the observation that RSV antibody complexes induced the release of significant quantities of thromboxane B₂ from neutrophils as determined by radioimmunoassay. Oxygen radicals and/or products of arachidonic acid metabolism may, in part, mediate the pathogenesis of RSV infection through direct tissue damage and bronchoconstriction.