OXYGEN-INDUCED LUNG INJURY IN THE GUINEA-PIG PROCEEDS THROUGH CD18-INDEPENDENT MECHANISMS

The pathogenesis of pulmonary oxygen toxicity is postulated to be rela ted in part to neutrophil-mediated injury. This study examined the eff ect of a monoclonal antibody directed against the CD11a,b,c/CD18 glyco protein complex (beta 2 leukocyte integrins) on oxygen-induced lung in jury. M8, a monoclonal antibody that binds to the beta chain of the gu inea pig leukocyte integrins that facilitate neutrophil adherence to v ascular endothelium, was injected into adult guinea pigs prior to and during exposure to > 98% oxygen. Control oxygen-exposed animals were i njected with a noninhibitory antibody to the CD18 complex or with sali ne. Survival in oxygen was similar for animals treated with M8 when co mpared with those treated with saline (102 versus 105 h, respectively, NS). Pulmonary edema as assessed by protein in the supernatant of bro nchoalveolar lavage fluid (BALF) was higher in the three groups of oxy gen-exposed animals than in the air-exposed groups (p < 0.01), but it did not differ between the M8 antibody treatment group and the other o xygen-exposed groups. M8 antibody treatment did not decrease hyperoxia -induced neutrophil accumulation into the lung as assessed by myeloper oxidase activity (MPO) in lung homogenates or by neutrophil counts in histologic specimens. M8 antibody also did not decrease neutrophil cou nts or MPO in alveolar lavage fluid, both of which were significantly elevated in all oxygen-exposed groups. These results suggest that hype roxia-induced neutrophil migration into the lung and acute lung injury occurs by CD18-independent processes in the guinea pig model of pulmo nary oxygen toxicity.