Requirements for L-selectin in neutrophil-mediated lung injury in rats.
L-selectin requirements in three models of acute lung injury in rats have been identified: systemic activation of complement after intravenous infusion of cobra venom factor (CVF) and intrapulmonary deposition of IgG or IgA immune complexes. In the CVF model of lung injury, treatment of rats with hamster monoclonal IgG anti-rat-L-selectin (HRL-1) induced significant neutropenia, necessitating the use of F(ab')2 fragments, which did not cause neutropenia. Treatment of rats with F(ab')2 anti-L-selectin (HRL-1) resulted in significant reductions in lung permeability and hemorrhage in the CVF model. Morphologically, this treatment 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 treatment with HRL-1. In both models protection was associated with reductions in lung myeloperoxidase content. Treatment of rats with a F(ab')2 form of hamster monoclonal IgG non-blocking anti-L-rat selectin, HRL-2, failed to show protective effects in the CVF and IgG immune complex models of lung injury. In the IgA immune complex model of injury, which is neutrophil-independent and related to toxic products from pulmonary macrophages, no protective effects of anti-L-selectin (HRL-1) were found. Therefore, in neutrophil-dependent and oxygen radical mediated lung injury, L-selectin plays a requisite role in tissue recruitment of neutrophils. In the neutrophil-independent model of lung injury, no requirement for L-selectin appears to exist.
Mulligan
M S
MS
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109.
Miyasaka
M
M
Tamatani
T
T
Jones
M L
ML
Ward
P A
PA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004546:Elapid Venoms; D007105:Immune Complex Diseases / Q000276:immunology; D019041:L-Selectin; D007958:Leukocyte Count; D008171:Lung Diseases / Q000276:immunology* / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D004546:Elapid Venoms; C016310:cobra venom factor; D019041:L-Selectin; D009195:Peroxidase