BLOOD MONOCYTE MIGRATION TO ACUTE LUNG INFLAMMATION INVOLVES BOTH CD11 CD18 AND VERY LATE ACTIVATION ANTIGEN-4-DEPENDENT AND INDEPENDENT PATHWAYS/

In acute lung inflammation, blood neutrophils and monocytes migrate in to the lung parenchyma and bronchoalveolar space. The infiltration of the inflamed lung by monocytes is poorly understood because of difficu lties in quantifying these cells in the presence of resident macrophag es. Radiolabeled monocytes were used to study monocyte migration into the inflamed rat lung, Monocytes and neutrophils were purified from bl ood, labeled with Cr-51 and In-111, respectively, and injected i.v. in to rats given an intratracheal injection of LPS. The accumulation of C r-51-labeled monocytes increased >10-fold in the lung parenchyma and 1 70-fold in the bronchoalveolar lavage (BAL) 18 h after LPS. In-111-lab eled neutrophils increased >30-fold in the lung tissue and 500-fold in the BAL. Treatment of rats with a blocking anti-CD18 mAb inhibited mo nocyte accumulation in the lung and BAL by about 30%, whereas blocking very late activation Ag-4 (VLA-4) had no effect. Combined blockade of VLA-4 and CD18 inhibited approximately 30% of the migration to the lu ng parenchyma, but decreased the BAL by 80%. Monocyte migration to cut aneous inflammation was completely abolished by the combined mAb treat ment. Neutrophil accumulation in the lung and BAL was not decreased by blocking either CD18 or VLA-4 and was only partially reduced by block ing CD18 plus VLA-4. Thus, monocyte migration to the LPS inflamed lung is substantially CD11/CD18 and VLA-4 independent, but accumulation in BAL is mediated by CD18 and VLA-4. Monocytes as well as neutrophils m ay use a previously unrecognized endothelial adhesion and migration pa thway in the lung.