Receptor-Mediated Modulation of Murine Mast Cell Function by α-Melanocyte Stimulating Hormone

Abstract

Abstract The proopiomelanocortin (POMC)-derived neuropeptide α-melanocyte stimulating hormone (α-MSH) is known to modulate some aspects of inflammation through direct effects on T cells, B cells, and monocytes. To determine whether α-MSH might similarly influence mast cell responsiveness, mast cells were examined to see if they expressed the receptor for α-MSH, melanocortin-1 (MC-1), and whether α-MSH altered mast cell function. We thus first identified MC-1 on bone marrow cultured murine mast cells (BMCMC) and a murine mast cell line (MCP-5) employing flow cytometry and through detection of specific binding. Subsequent treatment of mast cells with α-MSH increased the cAMP concentration in a characteristic biphasic pattern, demonstrating that α-MSH could affect intracellular processes. We next examined the effect of α-MSH on mediator release and cytokine expression. IgE/DNP-human serum albumin-stimulated histamine release from mast cells was inhibited by ∼60% in the presence of α-MSH. Although activation of BMCMC induced the expression of mRNAs for the inflammatory cytokines IL-1β, IL-4, IL-6, TNF-α, and the chemokine lymphotactin, mRNAs for IL-1β, TNF-α, and lymphotactin were down-modulated in the presence of α-MSH. Finally, IL-3-dependent proliferative activity of BMCMC was slightly but significantly augmented by α-MSH. Taken together, these observations suggest that α-MSH may exert an inhibitory effect on the mast cell-dependent component of a specific inflammatory response.