PUB - Publikationen an der Universität Bielefeld

a-Melanocyte-stimulating hormone (a-MSH) is released by immunocompetent cells as well as the pituitary gland and functions as a potent inhibitor of immune and inflammatory reactions. Therefore, it was investigated whether normal human monocytes express melanocortin (MC) receptors specific for a-MSH. Upon FACS analysis using biotin-labeled a-MSH, a low number of a-MSH binding sites was detectable on unstimulated monocytes. a-MSH receptor expression was up-regulated when monocytes were treated with endotoxin (LPS) or mitogen (PHA) for 3 to 5 days and was further augmented by the addition of cytokines such as IL-2, IFN-7, 11-4, and 11-10. Adrenocorticotropin, a precursor of a-MSH, but not the structurally unrelated /3-MSH, competitively inhibited a-MSH binding, suggesting that the receptor expressed on monocytes is specific for a-MSH. This was further confirmed by reverse transcription-PCR, which demonstrated that monocytes express mRNA specific for the MC receptor MC-1, which binds a-MSH and adrenocorticotropin, whereas mRNA specific for other known melanocortin receptors was not detectable. To investigate whether the immunosuppressing capacity of a-MSH is associated with the up-regulation of MC-1, its effect on the expression of costimulatory molecules (CD86 and CD80) on human monocytes was investigated. a-MSH significantly inhibited the expression of CD86 on LPS-treated monocytes, which exhibited a high density of MC-1, whereas CD80 expression was not altered. These findings indicate that human monocytes, depending on their activation and maturation state, are able to express MC-1, and up-regulation of MC-1 seems to be required to enable a-MSH to modulate immune responses in which costimulatory molecules play a decisive role.