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Evidence for the differential expression of the functional alpha-melanocyte-stimulating hormone receptor MC-1 on human monocytes.

R Bhardwaj, E Becher, K Mahnke, M Hartmeyer, T Schwarz, T Scholzen and T A Luger
J Immunol April 1, 1997, 158 (7) 3378-3384;
R Bhardwaj
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E Becher
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K Mahnke
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M Hartmeyer
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T Schwarz
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T Scholzen
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T A Luger
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Abstract

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.

  • Copyright © 1997 by American Association of Immunologists

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The Journal of Immunology
Vol. 158, Issue 7
1 Apr 1997
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Evidence for the differential expression of the functional alpha-melanocyte-stimulating hormone receptor MC-1 on human monocytes.
R Bhardwaj, E Becher, K Mahnke, M Hartmeyer, T Schwarz, T Scholzen, T A Luger
The Journal of Immunology April 1, 1997, 158 (7) 3378-3384;

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Evidence for the differential expression of the functional alpha-melanocyte-stimulating hormone receptor MC-1 on human monocytes.
R Bhardwaj, E Becher, K Mahnke, M Hartmeyer, T Schwarz, T Scholzen, T A Luger
The Journal of Immunology April 1, 1997, 158 (7) 3378-3384;
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Print ISSN 0022-1767        Online ISSN 1550-6606