MULTIFUNCTIONAL CYTOKINE EXPRESSION BY HUMAN MAST-CELLS - REGULATION BY T-CELL MEMBRANE CONTACT AND GLUCOCORTICOIDS

Human mast cells readily release a variety of mediators, including cyt okines, in response to IgE receptor crosslinking, but the mechanisms g overning the expression of cytokines are still unclear. Using a human mast cell line, HMC-1, we show expression of cytokine transcripts as e arly as 2 h after activation with ionomycin and phorbol myristate acet ate (PMA). Resting HMC-1 cells expressed transcripts for interleukin-l receptor antagonist (IL-1RA), IL-2, IL-4, IL-5, GM-CSF, and weakly fo r IL-8, and stimulation with ionomycin and PMA induced additional tran scripts for IL-6 and IL-13 and upregulated expression of IL-8 transcri pts. HMC-1 cells secreted IL-4, IL-8, and GM-CSF protein after activat ion and dexamethasone significantly inhibited the production of these cytokines. Of significance is the finding that the addition of membran es purified from activated T cells to mast cell cultures induced trans cripts selectively for IL-8 and none for other proinflammatory cytokin es. Flow cytometry revealed that resting HMC-1 cells express CD40, a m olecule involved in contact-dependent signaling of monocytes and B cel ls by T cells. However, activation of HMC-1 by anti-CD40 antibody did not induce IL-8 gene expression or protein production. This study demo nstrates that human mast cells are capable of expressing multiple cyto kines that can be inhibited by glucocorticoids. It also raises the pos sibility that T cells may activate mast cell cytokine synthesis by nov el contact-dependent mechanisms. This phenomenon of T cell regulation of mast cell function requires further study.