Macrophage Inflammatory Proteins 1 and 2: Expression by Rat Alveolar Macrophages, Fibroblasts, and Epithelial Cells and in Rat Lung after Mineral Dust Exposure

Abstract Macrophage inflammatory proteins 1α and 2 (MIP-1α, MIP-2) are members of a growing family of cytokines thought to play a role in host defense. MIP-1α and MIP-2 were previously identified in the mouse and shown to stimulate inflammatory cell recruitment. To better understand the potential role of MIP-1α and MIP-2 in lung defense, we investigated the ability of rat lung cells to express mRNA for and/or secrete MIP-1α and MIP-2 proteins in vitro and characterized expression of these cytokines in rat lung after in vivo exposure to silica (SiO2) or titanium dioxide (TiO2). In response to lipopolysaccharide, rat alveolar macrophages expressed increased levels of MIP-1α and MIP-2 mRNA and secreted proteins (identified by N-terminal sequencing) homologous to mouse MIP-1α and MIP-2. Rat alveolar macrophage MIP-1α and MIP-2 mRNA expression was also increased by tumor necrosis factor-α (TNF) and adherence to plastic. Studies with a rat fibroblast and epithelial cell line demonstrated that MIP-2, but not MIP-1α, expression can be detected in these cells after stimulation with TNF. Intratracheal instillation studies with SiO2 and TiO2 showed that inflammatory doses of these dusts increase MIP-1α and MIP-2 mRNA expression in whole lung and that increased gene expression preceded the accumulation of inflammatory cells. These results demonstrate that MIP-1α and MIP-2 cytokines are expressed in the rat and further support the concept that, in addition to macrophages, tissue structural cells (i.e., fibroblasts, epithelial cells) may play a key role as effectors of inflammatory cell recruitment through elaboration of chemotactic cytokines. The demonstration that mineral dust exposure increases expression of MIP-1α and MIP-2 in lung tissue suggests these cytokines are responsible, at least in part, for recruitment of inflammatory cells after particle deposition or lung tissue in jury.