NOVEL ROLE OF TRANSMEMBRANE SCP FOR MAST-CELL ACTIVATION AND EOTAXIN PRODUCTION IN MAST-CELL FIBROBLAST INTERACTIONS

Mast cell activation can be induced by multiple mechanisms, including IgE-, complement-, and stem cell factor (SCF)-mediated pathways. In ad dition, the interaction of mast cells with particular cell populations , such as fibroblasts, have also demonstrated increased mast cell reac tivity, In these studies, we have investigated the role of fibroblast- mast cell interaction for induction of histamine release and chemokine production and the specific role of SCF during this interaction. Prim ary pulmonary fibroblast cell lines were grown in culture and used thr oughout these studies. Mast cells were grown in parallel,vith fibrobla sts by incubation of bone marrow cells with SCF and IL-3, During mast cell-fibroblast coculture, increased histamine release could be attenu ated either by separation of the cell populations using a Trans-Well s etup, which did not allow cellular contact, or by specific anti-SCF Ab , In addition, a significant increase in eotaxin, a potent eosinophil- specific C-C chemokine, was also observed during fibroblast-mast cell interaction. The production of eotaxin was cell contact dependent and could be inhibited using an anti-SCF Ab or specific antisense therapy. SCF was constitutively produced from fibroblasts in its transmembrane form and could be induced by TNF, SCF-coated plates induced significa nt mast cell-derived eotaxin production, whereas soluble SCF induced l ittle or no eotaxin, suggesting a necessity for receptor cross-linking for activation. These studies indicate that fibroblast-mast cell cont act plays a role in exacerbation of histamine release and eotaxin prod uction.