Asahina A, Hosoi J, Beissert S, Stratigos A, Granstein R D
Department of Dermatology, Massachusetts General Hospital, Charlestown 02129.
J Immunol. 1995 Apr 1;154(7):3056-61.
Calcitonin gene-related peptide (CGRP)-containing nerves are frequently associated anatomically with epidermal Langerhans cells (LC), and LC Ag-presenting function is down-regulated by CGRP. To investigate possible regulation of cutaneous immunity by CGRP, we examined its effect on the induction of delayed-type hypersensitivity (DTH) and contact hypersensitivity (CHS). A system of immunity to the murine spindle cell tumor S1509a (H-2a) was employed to examine induction of DTH by LC. This system requires exposure of epidermal cells (EC) to GM-CSF for induction of substantial immunity. EC were prepared from CAF1 mice (H-2a/d) and Thy-1+ cells deleted. EC were exposed for 16 h to GM-CSF with or without CGRP. EC were then pulsed with tumor-associated Ags (TAA), washed, and injected s.c. into mice three times at 7-day intervals for immunization. Mice were challenged for a DTH response by injection of a hind footpad with TAA-pulsed EC, and 24-h footpad swelling assessed. Exposure of EC to CGRP significantly inhibited induction of DTH. To examine the effect of CGRP administered in vivo on induction of immunity, 530 pmol of CGRP or diluent alone was injected intradermally into the dorsum of the left ear of naive mice 8 h and 3 h before epicutaneous application of a hapten at the injected site. Mice were challenged on the right ear 7 days later and 24 h ear swelling was assessed. CGRP significantly inhibited the induction of CHS whereas calcitonin had no effect. Furthermore, when hapten was applied at a site distant from CGRP administration, no inhibition of CHS was observed, suggesting that the effect of CGRP is local. These data support the concept that CGRP may be an endogenous regulator of immune function and also suggest the possibility that CGRP or its analogues administered in vivo might have therapeutic utility as immunomodulators.
含降钙素基因相关肽（CGRP）的神经在解剖学上常与表皮朗格汉斯细胞（LC）相关联，且CGRP可下调LC的抗原呈递功能。为研究CGRP对皮肤免疫的可能调节作用，我们检测了其对迟发型超敏反应（DTH）和接触性超敏反应（CHS）诱导的影响。采用针对小鼠梭形细胞瘤S1509a（H-2a）的免疫体系来检测LC对DTH的诱导作用。该体系需要将表皮细胞（EC）暴露于粒细胞-巨噬细胞集落刺激因子（GM-CSF）以诱导显著的免疫反应。EC取自CAF1小鼠（H-2a/d）并去除Thy-1+细胞。将EC与或不与CGRP一起暴露于GM-CSF 16小时。然后用肿瘤相关抗原（TAA）脉冲处理EC，洗涤后，以7天的间隔皮下注射到小鼠体内三次进行免疫。通过向后足垫注射TAA脉冲处理的EC来激发小鼠的DTH反应，并评估24小时后足垫肿胀情况。EC暴露于CGRP显著抑制了DTH的诱导。为检测体内给予CGRP对免疫诱导的影响，在皮肤致敏剂经皮应用于注射部位前8小时和3小时，将530皮摩尔的CGRP或单独的稀释剂皮内注射到未致敏小鼠的左耳背。7天后对小鼠右耳进行激发，并评估24小时后耳肿胀情况。CGRP显著抑制了CHS的诱导，而降钙素则无此作用。此外，当在远离CGRP给药部位应用致敏剂时，未观察到对CHS的抑制作用，这表明CGRP的作用是局部的。这些数据支持CGRP可能是免疫功能的内源性调节因子这一概念，也提示体内给予CGRP或其类似物作为免疫调节剂可能具有治疗用途。
