Faculty of Health and Life Sciences, Centre for Research in Biosciences, University of the West of England, Frenchay, Bristol, UK.
Int Immunopharmacol. 2012 Sep;14(1):75-81. doi: 10.1016/j.intimp.2012.06.011. Epub 2012 Jun 22.
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.
肾上腺髓质素（AM）是一种新型血管扩张肽，主要通过降钙素受体样受体（CLR）与受体活性修饰蛋白（RAMP）2 或 3 结合（分别形成 AM（1）和 AM（2）受体）发挥作用。AM 在炎症过程中发挥重要作用，其表达在细胞因子治疗后增加，促进原位巨噬细胞作用，并在缺氧条件下高表达 T 细胞。以前对 T 细胞 AM 受体表达的检查并不完整，因此我们在此考虑 AM 受体的表达及其对 AM 和糖皮质激素（GC）的反应性。通过 PCR 和流式细胞术检查原代人 T 细胞中的 AM 受体表达，发现未刺激的 T 细胞中生理表达 RAMP2、3 和 CLR，无论是在细胞内还是在细胞表面。PHA 刺激可降低受体蛋白，CLR 和 RAMP3 降低尤为明显。AM 孵育引起的受体改变有限，但 GC 处理（10（-6）M；24 小时）显著影响细胞表面表达，在未刺激细胞中显著增加受体成分，在刺激的 T 细胞中显著减少相同成分。我们的发现表明，人 T 细胞利用 AM（1）和 AM（2）受体，它们以激活状态依赖性方式对 GC 敏感。
