Evidence for the differential expression of the functional alpha-melanocyte-stimulating hormone receptor MC-1 on human monocytes.
alpha-Melanocyte-stimulating hormone (alpha-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 alpha-MSH. Upon FACS analysis using biotin-labeled alpha-MSH, a low number of alpha-MSH binding sites was detectable on unstimulated monocytes. alpha-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-gamma, IL-4, and IL-10. Adrenocorticotropin, a precursor of alpha-MSH, but not the structurally unrelated beta-MSH, competitively inhibited alpha-MSH binding, suggesting that the receptor expressed on monocytes is specific for alpha-MSH. This was further confirmed by reverse transcription-PCR, which demonstrated that monocytes express mRNA specific for the MC receptor MC-1, which binds alpha-MSH and adrenocorticotropin, whereas mRNA specific for other known melanocortin receptors was not detectable. To investigate whether the immunosuppressing capacity of alpha-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. alpha-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 alpha-MSH to modulate immune responses in which costimulatory molecules play a decisive role.
Bhardwaj
R
R
Department of Dermatology, University of Munster, Germany.
Becher
E
E
Mahnke
K
K
Hartmeyer
M
M
Schwarz
T
T
Scholzen
T
T
Luger
T A
TA
D001665:Binding Sites; D006801:Humans; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012194:RNA-Directed DNA Polymerase; D018043:Receptors, Corticotropin / Q000032:analysis / Q000096:biosynthesis*; D044101:Receptors, Melanocortin; D000521:alpha-MSH / Q000378:metabolism* / Q000494:pharmacology
D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D000521:alpha-MSH; D012194:RNA-Directed DNA Polymerase