Receptor-mediated modulation of murine mast cell function by alpha-melanocyte stimulating hormone.
The proopiomelanocortin (POMC)-derived neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) is known to modulate some aspects of inflammation through direct effects on T cells, B cells, and monocytes. To determine whether alpha-MSH might similarly influence mast cell responsiveness, mast cells were examined to see if they expressed the receptor for alpha-MSH, melanocortin-1 (MC-1), and whether alpha-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 alpha-MSH increased the cAMP concentration in a characteristic biphasic pattern, demonstrating that alpha-MSH could affect intracellular processes. We next examined the effect of alpha-MSH on mediator release and cytokine expression. IgE/DNP-human serum albumin-stimulated histamine release from mast cells was inhibited by approximately 60% in the presence of alpha-MSH. Although activation of BMCMC induced the expression of mRNAs for the inflammatory cytokines IL-1beta, IL-4, IL-6, TNF-alpha, and the chemokine lymphotactin, mRNAs for IL-1beta, TNF-alpha, and lymphotactin were down-modulated in the presence of alpha-MSH. Finally, IL-3-dependent proliferative activity of BMCMC was slightly but significantly augmented by alpha-MSH. Taken together, these observations suggest that alpha-MSH may exert an inhibitory effect on the mast cell-dependent component of a specific inflammatory response.
Adachi
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Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Nakano
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Vliagoftis
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Metcalfe
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D000818:Animals; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation / Q000276:immunology; D006636:Histamine Release; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018043:Receptors, Corticotropin / Q000096:biosynthesis / Q000502:physiology*; D044101:Receptors, Melanocortin; D000521:alpha-MSH / Q000378:metabolism / Q000502:physiology*
D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D000521:alpha-MSH; D000242:Cyclic AMP