CINC/gro and MCP-1 induce CD18-dependent neutrophil migration from inflamed venules in vivo

In a model of adjuvant-induced vasculitis, we have reported a large increase in leukocyte trafficking within mesenteric postcapillary venules (J.Exp.Med. 183:1995). However, leukocyte emigration from these vessels was very low. In this study we examined the adhesion molecules that mediate transendothelial leukocyte migration in response to the C-X-C chemokine CINC/gro and the C-C chemokine MCP-1. CINC/gro (1 nM) and MCP-1 (1 ng/ml) did not elicit leukocyte diapedesis in the mesentery of control rats, but caused large increases in leukocyte diapedesis in adjuvant-immunized rats (MCP-1: 61.8±9.8, CINC/gro:101.3±8.5 cells/field). Histology revealed that the majority of the recruited leukocytes were neutrophils. Moreover, an anti-neutrophil serum significantly reduced both MCP-1 (18.3±4.8 cells/field) and CINC/gro-induced (29.7±8.2 cells/field) leukocyte emigration. An anti-CD18 antibody almost completely blocked MCP-1-induced leukocyte emigration (9.0±1.0 cells/field), but did not affect leukocyte adhesion. An antibody against the ∝₄-integrin (CD49d) reduced both adhesion and emigration (22.0±17.5 cells/field). This study demonstrates that both C-X-C and C-C chemokines can recruit neutrophils in vivo, and that CD18 is required for transendothelial migration independent from its usual role in leukocyte adhesion.