Macrophage/fibroblast coculture induces macrophage inflammatory protein-1α production mediated by intercellular adhesion molecule-1 and oxygen radicals

This study examined the cell-to-cell interaction between fibroblasts and macrophages as a possible contributor to the chronic inflammatory state. In a coculture system, consisting of macrophages layered over confluent fibroblasts, there was a significant increase in macrophage inflammatory protein 1alpha (MIP-1alpha) compared with control cultures. ICAM-1 adhesion was identified as an important stimulus of MIP-1alpha production by using ICAM-1-specific monoclonal antibodies. Furthermore, fibroblasts from ICAM-1 knockout mice induced significantly less MIP-1alpha production from peritoneal macrophages when compared to control fibroblasts. In addition, it appeared that oxygen radicals functioned as activating molecules during cellular interaction and production of MIP-1alpha, as the addition of the antioxidant N-acetylcysteine (NAC) prevented MIP-1alpha secretion. Thus, the ICAM-1 and oxygen radical-mediated induction of MIP-1alpha 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.