Asahina A, Moro O, Hosoi J, Lerner E A, Xu S, Takashima A, Granstein R D
MGH/Harvard Cutaneous Biology Research Center, Massachusetts General Hospital, Boston 02114, USA.
Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8323-7. doi: 10.1073/pnas.92.18.8323.
Epidermal Langerhans cells (LC) are associated anatomically with epidermal nerves, and a product of these nerves, calcitonin gene-related peptide (CGRP), inhibits the antigen-presenting capacity of LC and macrophages. As the CGRP receptor appears to be coupled to Gs alpha protein, which in turn activates adenylate cyclase, the ability of CGRP to induce cAMP in LC was examined and correlated with functional effects. LC were isolated from murine epidermal cells using antibodies on magnetic microspheres. Exposure to CGRP induced a significant increase in cAMP content, which could be inhibited by coculture with a truncated form of CGRP [CGRP-(8-37)] that is a specific competitive inhibitor of CGRP. Substance P and calcitonin failed to induce cAMP in LC. Although culture in CGRP reduced the ability of murine epidermal cells enriched for LC content to present pigeon cytochrome c to a responsive clone or to present antigen for elicitation of delayed-type hypersensitivity in immune mice, culture in forskolin had little or no effect on antigen presentation despite increased cAMP content of LC as much or more than that induced by CGRP. The effect of CGRP on antigen presentation in these systems could be blocked with CGRP-(8-37). CGRP inhibited the induction of B7-2 by lipopolysaccharide on peritoneal macrophages and a LC line, whereas calcitonin did not. CGRP induces specific accumulation of cAMP in LC and inhibits LC antigen-presenting function by a receptor-mediated event. However, the induction of cAMP by itself does not account for inhibition of antigen presentation. Suppression of the expression of B7-2 may be one mechanism by which CGRP inhibits antigen presentation.
表皮朗格汉斯细胞（LC）在解剖学上与表皮神经相关，这些神经的一种产物——降钙素基因相关肽（CGRP），可抑制LC和巨噬细胞的抗原呈递能力。由于CGRP受体似乎与Gsα蛋白偶联，而Gsα蛋白又激活腺苷酸环化酶，因此研究了CGRP在LC中诱导cAMP的能力，并将其与功能效应相关联。使用磁珠上的抗体从鼠表皮细胞中分离出LC。暴露于CGRP会导致cAMP含量显著增加，而与CGRP的特异性竞争性抑制剂——截短形式的CGRP [CGRP-(8-37)] 共培养可抑制这种增加。P物质和降钙素未能在LC中诱导cAMP。尽管在CGRP中培养会降低富含LC的鼠表皮细胞将鸽细胞色素c呈递给反应性克隆或呈递抗原以引发免疫小鼠迟发型超敏反应的能力，但尽管LC的cAMP含量增加程度与CGRP诱导的相当或更高，福斯可林培养对抗原呈递几乎没有影响。CGRP对这些系统中抗原呈递的影响可用CGRP-(8-37)阻断。CGRP抑制脂多糖对腹膜巨噬细胞和LC系中B7-2的诱导，而降钙素则无此作用。CGRP通过受体介导的事件在LC中诱导cAMP的特异性积累并抑制LC抗原呈递功能。然而，cAMP的诱导本身并不能解释对抗原呈递的抑制作用。B7-2表达的抑制可能是CGRP抑制抗原呈递的一种机制。
