alpha-Melanocyte stimulating hormone acts as a selective inducer of secretory functions in human mast cells.

In the present study, we have investigated the pro-opiomelanocortin (POMC)-derived neuropeptide alpha-MSH for its ability to modulate activation of human mast cells. The in vitro ability of purified human skin mast cells to secrete various types of mast cell mediators was monitored in response to alpha-MSH at the mRNA and at the protein level. Picomolar concentrations of alpha-MSH induced a dose-dependent release of histamine from isolated human skin mast cells and from skin punch biopsies. However, no effect of alpha-MSH was seen regarding the expression of IL-1, IL-6, IL-8, TGF-beta, and TNF-alpha. Melanocortin receptor MC-1 was identified at the transcriptional level by RT-PCR analysis but not at the protein level, whereas, in leukemic human mast cells (HMC-1), the mRNAs and the proteins for the MC-1 and MC-5 receptor were identified. These results suggest that alpha-MSH may selectively induce acute inflammatory effects via secretion of histamine.

[1]  J. M. Lipton,et al.  Mechanisms of Antiinflammatory Action of α‐MSH Peptides: In Vivo and in Vitro Evidence , 1999 .

[2]  T. Luger,et al.  Expression of MC1‐ and MC5‐Receptors on the Human Mast Cell Line HMC‐1 , 1999, Annals of the New York Academy of Sciences.

[3]  A. Mauviel,et al.  The Role of Proopiomelanocortin‐Derived Peptides in Skin Fibroblast and Mast Cell Functions , 1999, Annals of the New York Academy of Sciences.

[4]  D. Metcalfe,et al.  Receptor-mediated modulation of murine mast cell function by alpha-melanocyte stimulating hormone. , 1999, Journal of immunology.

[5]  A. Buku.  Mast cell degranulating (MCD) peptide: a prototypic peptide in allergy and inflammation , 1999, Peptides.

[6]  T. Baumruker,et al.  TNF–· and IL–5 Gene Induction in IgE plus Antigen–Stimulated Mast Cells Require Common and Distinct Signaling Pathways , 1999, International Archives of Allergy and Immunology.

[7]  J. Buggy.  Binding of alpha-melanocyte-stimulating hormone to its G-protein-coupled receptor on B-lymphocytes activates the Jak/STAT pathway. , 1998, The Biochemical journal.

[8]  J. M. Lipton,et al.  Anti-inflammatory actions of the neuroimmunomodulator α-MSH , 1997 .

[9]  T. Luger,et al.  The Role of α-Melanocyte-Stimulating Hormone in Cutaneous Biology , 1997 .

[10]  C. Tsigos,et al.  Receptors for Melanocortin Peptides in the Hypothalamic‐Pituitary‐Adrenal Axis and Skin , 1995, Annals of the New York Academy of Sciences.

[11]  Y. Konda,et al.  Interaction of dual intracellular signaling pathways activated by the melanocortin-3 receptor. , 1994, The Journal of biological chemistry.

[12]  D. Schadendorf,et al.  Human mast cells produce IL-8. , 1993, Journal of immunology.

[13]  A. Thody,et al.  Alpha-melanocyte-stimulating hormone stimulates protein kinase C activity in murine B16 melanoma. , 1992, The Journal of endocrinology.

[14]  G. Trinchieri,et al.  Human dermal mast cells contain and release tumor necrosis factor alpha, which induces endothelial leukocyte adhesion molecule 1. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[15]  B. Beer,et al.  Mast Cell Degranulating Peptide: A Multi‐functional Neurotoxin , 1990, The Journal of pharmacy and pharmacology.

[16]  G. Dewald,et al.  Establishment of an immature mast cell line from a patient with mast cell leukemia. , 1988, Leukemia research.

[17]  R. Farese,et al.  Dual activation of the inositol-triphosphate-calcium and cyclic nucleotide intracellular signaling systems by adrenocorticotropin in rat adrenal cells. , 1986, Biochemical and biophysical research communications.

[18]  B. Mackler,et al.  Further studies on the structural requirements for polypeptide-mediated histamine release from rat mast cells. , 1979, The Biochemical journal.