Human Mast Cells Release Oncostatin M (OSM) Specifically on Contact with Activated T Cells

Abstract

RATIONALE: We have recently demonstrated that mast cells can be activated by heterotypic adhesion to activated T cells. In an effort to systematically examine the cytokine genes that are up-regulated on activation of mast cells, we used microarray analysis to perform gene expression profiling on human mast cells activated by either IgE-cross-linking or by T cells. We further characterized one of the cytokines, which was specifically up-regulated on T cell-induced mast cell activation, OSM. METHODS: Expression of OSM was validated by RT-PCR and the released protein measured by ELISA in both the LAD 2 human mast cell line and in cord blood-derived human mast cells. Immunocytochemistry was used to localize OSM in human mast cells. The biological activity of mast cell-derived OSM was verified by its effect on the proliferation of human lung fibroblasts. RESULTS: OSM was found to be expressed and released specifically on T cell-induced mast cell activation but not on IgE cross-linking. OSM was localized to the cytoplasm and its production inhibited by dexamethasone. Mast cell derived OSM was also found to be biologically active in inducing lung fibroblast proliferation that was partially but significantly inhibited by anti OSM mAb. CONCLUSIONS: Based on the previously reported biological effects of OSM, our results suggest that the (here-to-fore unknown) production of OSM by human mast cells may represent one link between T cell-induced mast cell activation and the development of a spectrum of structural changes in T cell-mediated inflammatory processes in which mast cells have been found to be involved.