Adrenomedullin receptors on human T cells are glucocorticoid-sensitive.
Adrenomedullin (AM) is a novel vasodilatatory peptide which acts primarily through the calcitonin receptor-like receptor (CLR) in combination with either receptor-activity-modifying-protein (RAMP) 2 or 3 (forming receptors, AM(1) and AM(2) respectively). AM plays an important role during inflammation, with its expression increasing following cytokine treatment, promoting macrophage action in situ and high expression by T cells during hypoxic conditions. Examination of T cell AM receptor expression has previously been incomplete, hence we here consider the presentation of AM receptors and their responsiveness to AM and glucocorticoids (GC). AM receptor expression was examined by PCR and flow cytometry in primary human T cells, revealing that RAMP2, 3 and CLR are physiologically expressed in unstimulated T cells, both intracellularly and on the cell surface. PHA stimulation decreased receptor proteins, significantly so for CLR and RAMP3. Incubation with AM elicited limited receptor alterations however, GC treatment (10(-6) M; 24 h) markedly affected cell surface expression, significantly increasing receptor components in unstimulated cells and significantly decreasing the same in stimulated T cells. Our findings indicate that human T cells utilize both AM(1) and AM(2) receptors, which are GC-sensitive in an activation-state dependent manner.
Faculty of Health and Life Sciences, Centre for Research in Biosciences, University of the West of England, Frenchay, Bristol, UK. eliliverani@temple.edu
Elisabetta
E
Liverani
Julie D
JD
McLeod
Carolyn
C
Paul
D053607:Adrenomedullin / Q000494:pharmacology; D058286:Calcitonin Receptor-Like Protein / Q000235:genetics / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D058263:Receptor Activity-Modifying Protein 2 / Q000235:genetics / Q000378:metabolism; D058264:Receptor Activity-Modifying Protein 3 / Q000235:genetics / Q000378:metabolism; D058265:Receptors, Adrenomedullin / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D058286:Calcitonin Receptor-Like Protein; C545503:RAMP2 protein, human; C545504:RAMP3 protein, human; D058263:Receptor Activity-Modifying Protein 2; D058264:Receptor Activity-Modifying Protein 3; D058265:Receptors, Adrenomedullin; D053607:Adrenomedullin; D003907:Dexamethasone; D000242:Cyclic AMP