MC1 receptors are constitutively expressed on leucocyte subpopulations with antigen presenting and cytotoxic functions

Abstract

The expression of melanocortin MC(1) receptors on human peripheral lymphocyte subsets was analysed by flow cytometry using rabbit antibodies selective for the human MC(1) receptor and a panel of monoclonal antibodies against lymphocyte differentiation markers. The MC(1) receptor was found to be constitutively expressed on monocytes/macrophages, B-lymphocytes, natural killer (NK) cells and a subset of cytotoxic T-cells. Interestingly T-helper cells appeared to be essentially devoid of MC(1) receptors. The results were confirmed by RT-PCR which indicated strong expression of MC(1) receptor mRNA in CD14(+), CD19(+) and CD56(+) cells. However, only a faint RT-PCR signal was seen in CD3(+) cells, in line with the immuno-staining results that indicated that only part of the CD3(+) cells (i.e. some of the CD8(+) cells) expressed the MC(1) receptor. The MC(1) receptors' constitutive expression on immune cells with antigen-presenting and cytotoxic functions implies important roles for the melanocortic system in the modulation of immune responses.

α-Melanocyte-stimulating Hormone Inhibits Lipopolysaccharide-induced Tumor Necrosis Factor-α Production in Leukocytes by Modulating Protein Kinase A, p38 Kinase, and Nuclear Factor κB Signaling Pathways

“…However, the molecular mechanisms of these ␣-MSH anti-inflammatory effects have not been defined previously. MC 1 R is constitutively expressed in monocytes and subpopulations of lymphocytes and plays an important role in the anti-inflammatory action of ␣-MSH (19,39). Here, we found that PMA-treated THP-1 cells express significantly more MC 1 R when compared with Me 2 SOtreated HL-60 cells.…”

The immunomodulating neuropeptide alpha-melanocyte-stimulating hormone (α-MSH) suppresses LPS-stimulated TLR4 with IRAK-M in macrophages

“…How α-MSH treatment can lead to IRAK-M binding of IRAK-1 is not addressed by our findings, and how this can happen is complicated by the expression of three melanocortin receptors (MC1r, MC3r, and MC5r) that bind α-MSH on macrophages (Getting et al, 1999;Neumann Andersen et al, 2001;Taherzadeh et al, 1999). In general, the melanocortin receptors are G-protein coupled and are not evenly distributed throughout the body.…”

“…In general, the melanocortin receptors are G-protein coupled and are not evenly distributed throughout the body. The most predominate melanocortin receptor on macrophages and dendritic cells is MC1r (Neumann Andersen et al, 2001), although message for MC3r and MC5r can be detected (Taherzadeh et al, 1999). The engagement of α-MSH with MC1r elevates cAMP levels in the macrophages and activates a cAMP-dependent protein kinase A (PKA; Yoon et al, 2003).…”

Redundancy of a Functional Melanocortin 1 Receptor in the Anti-inflammatory Actions of Melanocortin Peptides: Studies in the Recessive Yellow (e/e) Mouse Suggest an Important Role for Melanocortin 3 Receptor

“…MC1-R mRNA, but not protein, expression has been found on monocytes, B lymphocytes, NK cells, a subset of cytoxic T cells (4), dendritic cells (5), and more recently mast cells (6). MC1-Rmediated anti-inflammatory effects appear to occur via inhibition of NF-B activation (7,8) and protection of IB␣ degradation (9).…”