Functional roles of MCP-1 in Propionibacterium acnes-induced, T cell-mediated pulmonary granulomatosis in rabbits

The immunological manifestation of granuloma formations in humans largely depends on the delayed-type hypersensitivity response, We investigated the involvement of monocyte chemoattractant protein-1 (MCP-1) in a rabbit model of T cell-mediated pulmonary granulomatosis. Intravenous injection of Propionibacterium acnes (P, acnes) into sensitized rabbits induced massive and diffuse pulmonary granulomas. Levels of MCP-1 in sera and bronchoalveolar lavage fluids (BALF) peaked before the granuloma formation reached the peak (on days 1 and 3 after challenge, respectively), Chemotactic activities toward monocytes and T cells in BALF were inhibited by anti-MCP-1 IgG by 80 and 36%, respectively, The phenotypic analysis of the migrating T cells revealed that activated and memory T cells rather than naive cells were preferentially attracted to the BALF, Administration of anti-MCP-l antiserum inhibited the development of granuloma formation ill both size and number, the numbers of infiltrating leukocytes int BALF, the expression of adhesion molecules on peripheral monocytes/T cells, and on macrophages/T cells inn BALF, and the production of TNF-alpha int the lung. Anti-MCP-1 resulted in a trend toward decreased level of IL-1 beta inn the lung. The inhibition of the production of these cytokines appeared to be induced indirectly through the inhibition of the recruitment of macrophages that produce these cytokines, The results suggest important roles of MCP-I 11 the development of granuloma formation in this model through the attraction and activation of specific types of cells.