The University of Southampton
University of Southampton Institutional Repository

?-Melanocyte-stimulating hormone suppresses antigen-induced lymphocyte proliferation in humans independently of melanocortin 1 receptor gene status

Cooper, Ashley, Robinson, Samantha J., Pickard, Chris, Jackson, Claire L., Friedmann, Peter S. and Healy, Eugene (2005) ?-Melanocyte-stimulating hormone suppresses antigen-induced lymphocyte proliferation in humans independently of melanocortin 1 receptor gene status Journal of Immunology, 175, (7), pp. 4806-4813.

Record type: Article

Abstract

Studies in mice indicate that ? -melanocyte-stimulating hormone (?MSH) is immunosuppressive, but it is not known whether ?MSH suppresses human immune responses to exogenous Ags. Human PBMCs, including monocytes, express the melanocortin 1 receptor (MC1R), and it is thought that the ability of ?MSH to alter monocyte-costimulatory molecule expression and IL-10 release is mediated by this receptor. However, the MC1R gene is polymorphic, and certain MC1R variants compromise receptor signaling via cAMP, resulting in red hair and fair skin. Here, we have investigated whether ?MSH can suppress Ag-induced lymphocyte proliferation in humans and whether these effects are dependent on MC1R genotype. ?MSH suppressed streptokinase-streptodornase-induced lymphocyte proliferation, with maximal inhibition at 10-¹³–10-¹¹ M ?MSH. Anti-IL-10 Abs failed to prevent suppression by ?MSH, indicating that it was not due to MC1R-mediated IL-10 release by monocytes. Despite variability in the degree of suppression between subjects, similar degrees of ?MSH-induced immunosuppression were seen in individuals with wild-type, heterozygous variant, and homozygous/compound heterozygous variant MC1R alleles. RT-PCR of streptokinase-streptodornase-stimulated PBMCs for all five melanocortin receptors demonstrated MC1R expression by monocytes/macrophages, MC1R and MC3R expression by B lymphocytes, but no melanocortin receptor expression by T lymphocytes. In addition, ?MSH did not significantly inhibit anti-CD3 Ab-induced lymphocyte proliferation, whereas ?MSH and related analogs (SHU9119 and MTII) inhibited Ag-induced lymphocyte proliferation in monocyte-depleted and B lymphocyte-depleted assays. These findings demonstrate that ?MSH, acting probably via MC1R on monocytes and B lymphocytes, and possibly also via MC3R on B lymphocytes, has immunosuppressive effects in humans but that suppression of Ag-induced lymphocyte proliferation by ?MSH is independent of MC1R gene status.

PDF 4806.pdf - Version of Record
Restricted to Repository staff only
Download (272kB)

More information

Published date: 1 October 2005

Identifiers

Local EPrints ID: 27002
URI: http://eprints.soton.ac.uk/id/eprint/27002
ISSN: 0022-1767
PURE UUID: 1745711e-f750-404a-a832-f259043e73e5

Catalogue record

Date deposited: 25 Apr 2006
Last modified: 17 Jul 2017 16:05

Export record

Contributors

Author: Ashley Cooper
Author: Samantha J. Robinson
Author: Chris Pickard
Author: Claire L. Jackson
Author: Peter S. Friedmann
Author: Eugene Healy

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×