REQUIREMENTS FOR L-SELECTIN IN NEUTROPHIL-MEDIATED LUNG INJURY IN RATS

L-selectin requirements in three models of acute lung injury in rats h ave been identified: systemic activation of complement after intraveno us infusion of cobra venom factor (CVF) and intrapulmonary deposition of IgG or IgA immune complexes. In the CVF model of lung injury, treat ment of rats with hamster monoclonal IgG anti-rat-L-selectin (HRL-1) i nduced significant neutropenia, necessitating the use of F(ab')2 fragm ents, which did not cause neutropenia. Treatment of rats with F(ab')2 anti-L-selectin (HRL-1) resulted in significant reductions in lung per meability and hemorrhage in the CVF model. Morphologically, this treat ment abrogated adhesive interactions of neutrophils with the pulmonary vascular endothelium. In the IgG immune complex model of injury, the parameters of injury were significantly reduced as a result of treatme nt with HRL-1. In both models protection was associated with reduction s in lung myeloperoxidase content. Treatment of rats with a F(ab')2 fo rm of hamster monoclonal IgG non-blocking anti-L-rat selectin, HRL-2, failed to show protective effects in the CVF and IgG immune complex mo dels of lung injury. In the IgA immune complex model of injury, which is neutrophilin-dependent and related to toxic products from pulmonary macrophages, no protective effects of anti-L-selectin (HRL-1) were fo und. Therefore, in neutrophil-dependent and oxygen radical mediated lu ng injury, L-selectin plays a requisite role in tissue recruitment of neutrophils. In the neutrophil-independent model of lung injury, no re quirement for L-selectin appears to exist.