COMPARTMENTALIZED ROLES FOR LEUKOCYTIC ADHESION MOLECULES IN LUNG INFLAMMATORY INJURY

By using the model of acute injury caused by intrapulmonary deposition of IgG immune complexes, blocking mAb to CD11a, CD11b, L-selectin, an d intercellular adhesion molecule-1 (ICAM-1) were administered either i.v. or intratracheally (i.t.). The effects of these interventions wer e assessed according to lung injury, lung content of myeloperoxidase ( MPO), TNF-alpha, and cellular content in bronchoalveolar lavage (BAL) fluids, and up-regulation of pulmonary vascular ICAM-1. In animals tre ated i.v. with Abs to CD11a, L-selectin, or ICAM-1 lung injury was sig nificantly attenuated in parallel with reduced lung content of MPO. Un der similar conditions, treatment with anti-CD11b had no effect. Howev er, when the same mAb were administered i.t., anti-CD11a and anti-L-se lectin were without protective effects, whereas i.t. administered anti -CD11b and anti-ICAM-1 were each highly protective. The protective eff ects of anti-CD11b were related to profound reductions in BAL levels o f TNF-alpha, pulmonary vascular up-regulation of ICAM-1, and lung cont ent of MPO. The protective effects of i.t.-administered anti-ICAM-1 we re not associated with reduced BAL levels of TNF-alpha. Protective eff ects of mAb were also reflected in reductions of retrievable neutrophi ls in BAL fluids. mAb to rat CD11b and CD18 but not to rat CD11a suppr essed in vitro production of TNF-alpha by immune complex-stimulated ra t alveolar macrophages. The mAb did not reduce NO2-/NO3- generation in stimulated macrophages but all mAb (except anti-ICAM-1) reduced O-2(- ) responses in macrophages. These data suggest a compartmentalized rol e for adhesion molecules in lung inflammatory injury after intraalveol ar deposition of IgG immune complexes, with CD11a, L-selectin, and ICA M-1 being important in the vascular compartment for neutrophil recruit ment, whereas in the alveolar compartment CD11b and ICAM-1 (but not CD 11a and L-selectin) seem to play key roles.