MACROPHAGE FIBROBLAST COCULTURE INDUCES MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA PRODUCTION MEDIATED BY INTERCELLULAR-ADHESION MOLECULE-1 AND OXYGEN RADICALS/

This study examined the cell-to-cell interaction between fibroblasts a nd macrophages as a possible contributor to the chronic inflammatory s tate. In a coculture system, consisting of macrophages layered over co nfluent fibroblasts, there tvas a significant increase in macrophage i nflammatory protein 1 alpha (MIP-1 alpha) compared with control cultur es. ICAM-1 adhesion was identified as an important stimulus of MIP-1 a lpha production by using ICAM-1-specific monoclonal antibodies. Furthe rmore, fibroblasts from ICAM-1 knockout mice induced significantly les s MIP-1 alpha production from peritoneal macrophages when compared to control fibroblasts. in addition, it appeared that oxygen radicals fun ctioned as activating molecules during cellular interaction and produc tion of MIP-1 alpha, as the addition of the antioxidant N-acetylcystei ne (NAC) prevented MIP-1 alpha secretion. Thus, the ICAM-1 and oxygen radical-mediated induction of MIP-1 alpha associated with a macrophage /fibroblast coculture system provides one possible mechanism by which immune/inflammatory cell interactions may augment chemokine production and exacerbate chronic inflammatory diseases.