Differential effects of CD18, CD29, and CD49 integrin subunit inhibition on neutrophil migration in pulmonary inflammation

Neutrophil migration to lung alveoli is a characteristic of lung diseases a nd is thought to occur primarily via capillaries rather than postcapillary venules, The role of adhesion molecules CD18 and CD29 on this migration in a mouse model of lung inflammation has been investigated. The number of neu trophils present in bronchoalveolar lavage fluid was determined 4 h after i ntratracheal instillation of LPS (0.1-1 mug) or murine recombinant KC (CXC chemokine, 0.03-0.3 mug). Both stimuli produced a dose-related increase in neutrophil accumulation, Intravenous anti-mouse CD18 mAb, 2E6 (0.5 mg/mouse ), significantly (p < 0.001) attenuated LPS (0.3 <mu>g)- but not KC (0.3 mu g)-induced neutrophil accumulation. The anti-mouse CD29 mAb, HM beta1-1 (0. 02 mg/mouse), significantly (p < 0.05) inhibited both LPS (0.3 <mu>g)- and KC (0.3 mug)-induced neutrophil migration, A second mAb to CD18 (GAME-46) a nd both F(ab')(2) and Feb of HM beta1-1 produced similar results to those a bove, while coadministration of mAbs did not result in greater inhibition. Electron microscopy studies showed that CD29 was involved in the movement o f neutrophils from the interstitium into alveoli. The effect of mAbs to CD4 9 (alpha integrin) subunits of CD29 was also examined. mAbs to CD49e and CD 49f inhibited both responses, while anti-CD49b and CD49d significantly inhi bited responses to KC only. These data suggest that CD29 plays a critical r ole in neutrophil migration in pulmonary inflammation and that CD49b and CD 49d mediate CD18-independent neutrophil accumulation.