SPECIFIC INDUCTION OF CAMP IN LANGERHANS CELLS BY CALCITONIN-GENE-RELATED PEPTIDE - RELEVANCE TO FUNCTIONAL-EFFECTS
SPECIFIC INDUCTION OF CAMP IN LANGERHANS CELLS BY CALCITONIN-GENE-RELATED PEPTIDE - RELEVANCE TO FUNCTIONAL-EFFECTS
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DOI：
10.1073/pnas.92.18.8323
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发表时间：
1995-08-29
影响因子：
11.1
通讯作者：
GRANSTEIN, RD
中科院分区：
文献类型：
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作者：
ASAHINA, A;MORO, O;GRANSTEIN, RD
表皮朗格汉斯细胞(LC)在解剖学上与表皮神经相关，其产物降钙素基因相关肽(CGRP)可抑制LC和巨噬细胞的抗原提呈能力。由于CGRP受体似乎与G(S)蛋白偶联，进而激活腺苷环化酶，因此我们检测了CGRP在LC中诱导cAMP的能力，并与其功能效应相关联。用磁性微球上的抗体从小鼠表皮细胞中分离出LC，暴露于CGRP可引起cAMP含量显著增加，cAMP含量可被CGRP的特异性竞争性抑制剂CGRP[CGRP-(8-37)]共同培养抑制，P物质和降钙素不能诱导LC中的cAMP，尽管在CGRP中培养降低了LC含量丰富的小鼠表皮细胞呈递鸽子细胞色素c到反应性克隆或呈递抗原的能力，以诱导小鼠迟发型超敏反应。福斯科林培养对抗原呈递几乎或没有影响，尽管LC中cAMP含量的增加与CGRP诱导的一样或更多。CGRP-(8-37)可阻断CGRP对这些系统的抗原提呈的影响。CGRP抑制脂多糖诱导的B7-2在巨噬细胞和一株LC细胞上的表达，而降钙素则不能，CGRP通过受体介导的事件诱导LC特异性积聚cAMP并抑制LC的抗原提呈功能，但cAMP本身的诱导不能解释其对抗原提呈的抑制作用，抑制B7-2的表达可能是CGRP抑制抗原提呈的机制之一。
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 G(s) a 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.