Endotoxin protection from oxygen toxicity: Effect on pulmonary neutrophils and L-selectin

The mechanisms by which sublethal doses of endotoxin protect against hyperoxic lung injury are not completely understood. We hypothesized that endotoxin treatment would result in a decreased inflammatory response to hyperoxia and that this would be accompanied by activation of neutrophils (as evidenced by loss of L-selectin) in the peripheral circulation. Adult rats were injected with endotoxin 0.5 mg/kg prior to and 24 hr after onset of exposure to ≥98% O₂. After 56 hr of hyperoxia, pulmonary neutrophils were lower in the O₂/endotoxin group compared to O₂ controls as measured by myeloperoxidase in lung homogenates and neutrophil counts in bronchoalveolar lavage fluid. Circulating neutrophils were also significantly lower in the O₂/endotoxin group compared to O₂ controls at 56 hr. Expression of the neutrophil adhesion molecule, L-selectin, was lower at 4 and 24 hr in the endotoxin-treated rats compared to O₂ controls. There were no differences at 48 hr. Expression of CD18 rose significantly in the O₂/endotoxin group after 4 hr, but thereafter did not differ from O₂ controls. In summary, endotoxin protection from O₂ toxicity was associated with reduced neutrophils in the lung and a loss of L-selectin from peripheral blood neutrophils.