SPECIFIC INDUCTION OF CAMP IN LANGERHANS CELLS BY CALCITONIN-GENE-RELATED PEPTIDE - RELEVANCE TO FUNCTIONAL-EFFECTS

Epidermal Langerhans cells (LC) are associated anatomically with epide rmal nerves, and a product of these nerves, calcitonin gene-related pe ptide (CGRP), inhibits the antigen-presenting capacity of LC and macro phages. As the CGRP receptor appears to be coupled to G(s) a protein, which in turn activates adenylate cyclase, the ability of CGRP to indu ce 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 cul ture in CGRP reduced the ability of murine epidermal cells enriched fo r LC content to present pigeon cytochrome c to a responsive clone or t o present antigen for elicitation of delayed-type hypersensitivity in immune mice, culture in forskolin had little or no effect on antigen p resentation despite increased cAMP content of LC as much or more than that induced by CGRP, The effect of CGRP on antigen presentation in th ese systems could be blocked with CGRP-(8-37). CGRP inhibited the indu ction 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 recepto r-mediated event, However, the induction of cAMP by itself does not ac count for inhibition of antigen presentation, Suppression of the expre ssion of B7-2 may be one mechanism by which CGRP inhibits antigen pres entation.