Reduction in inflammation following blockade of CD18 or CD29 adhesive pathways during the acute phase of a spirochetal-induced colitis in mice

Colitis develops in mice infected with Brachyspira (Serpulina) hyodysenteri ae. Numerous granulocytes (PMNs) are evident in cecal tissue sections 24-48 h post-infection. The role of PMNs was assessed by utilizing monoclonal an tibodies specific for CD18 or CD29 to block PMN recruitment. Macroscopic le sions were less severe in mice treated with either monoclonal antibody comp ared to lesions observed in isotype control-treated mice. While these monoc lonal antibodies may inhibit extravasation of other leukocytes, the central role of PMNs was further demonstrated in that colitis was reduced followin g neutrophil depletion. There was less edema and epithelial erosions in cec a of mice receiving anti-Ly6G, -CD18 or -CD29 monoclonal antibody compared to mice receiving the control. Moreover, there was a significant reduction in PMN infiltration in tissues of mice treated with anti-CD18. The reductio n in infiltrating PMNs did not result from downregulation of neutrophil che moattractant MIP-2 expression in anti-CD18-treated mice. In contrast, PMN r ecruitment into the cecum was apparently CD29-independent. It is noteworthy that the number of PMNs observed in anti-CD18-treated mice was significant ly higher than observed in non-infected mice. The data provide evidence for a threshold number of PMNs necessary for lesion development and indicate t hat CD18, but not CD29, adhesive pathways are crucial for PMN recruitment i n bacterial colitis. (C) 2000 Academic Press.