Antithrombin III diminishes production of oxygen radical in endotoxin-infused rat lung

The interaction of antithrombin III (AT) with cell surface glycosaminoglycans is known to have an inhibitory effect on inflammatory processes. We evaluated the effect of AT on endotoxin-induced production of oxygen radical in the pulmonary circulation using a fluorescent imaging technique. Also measured was the myeloperoxidase content of the lung, which served as an index of neutrophil accumulation, and neutrophil F-actin levels. Four groups of rats were infused for 2 h with endotoxin at 4.5 mg/kg/h (Et group), physiological saline (CT group), 100 U/kg of AT + endotoxin (AT group), or 100 U/kg of low-heparin-affinity latent-AT + endotoxin (L-AT group), respectively. Production of oxygen radical, neutrophil accumulation, and neutrophil F-actin levels were all significantly higher in the ET and L-AT groups than in the CT or AT group. Moreover; the levels of myeloperoxidase within the lung were well correlated with levels of oxygen radical production, which was consistent with the electron microscopic finding that cerium was deposited almost exclusively around neutrophils. Thus, it appears that AT most likely reduces F-actin formation in neutrophil by binding to glycosaminoglycans (e.g., syndecan-4) on the neutrophil, thereby reducing neutrophil accumulation in the lung, which would in turn inhibit oxygen radical production in the lung.