TRANSENDOTHELIAL MIGRATION AND TRAFFICKING OF LEUKOCYTES IN LFA-1-DEFICIENT MICE

The leukocyte integrin LFA-1 plays an important role in leukocyte traf ficking and the immune response. Using LFA-1-deficient mice, we demons trate that LFA-1 regulates the trafficking of lymphocytes to periphera l lymph nodes, and, to a lesser degree, to mesenteric lymph nodes and acute inflammatory sites. LFA-1, either because of its role in initial adhesion and/or the passage of leukocytes across endothelial cells, p lays a vital role in T lymphocyte and neutrophil transendothelial migr ation. Neutrophils and activated T lymphocytes from LFA-1-deficient mi ce were unable to cross endothelial cell monolayers in response to a c hemokine gradient, whereas wild-type (WT) T lymphocytes and neutrophil s were capable of migration. By contrast, LFA-1-deficient T lymphocyte s displayed normal chemotaxis to the same chemokine. Our studies with LFA-1-deficient monocytes indicate that LFA-1 acts in concert with com plement receptor 3 to mediate transendothelial migration of these cell s, as anti-CD18 monoclonal antibodies (mAb) blocked both WT and LFA-1- deficient monocyte transendothelial migration, whereas anti-CD11b mAb preferentially blocked transendothelial migration of LFA-1-deficient m onocytes. Finally, whereas anti-CD31 mAb blocked WT monocyte and neutr ophil transendothelial cell migration they did not block LFA-1-deficie nt monocyte and neutrophil transendothelial migration.