EXPRESSION OF NEUROTROPHIC FACTORS AND NEUROPEPTIDE RECEPTORS BY LANGERHANS CELLS AND THE LANGERHANS CELL-LIKE CELL-LINE XS52 - FURTHER SUPPORT FOR A FUNCTIONAL-RELATIONSHIP BETWEEN LANGERHANS CELLS AND EPIDERMAL NERVES

Epidermal Langerhans cells are frequently anatomically associated with calcitonin gene-related peptide-containing nerves. Furthermore, calci tonin gene-related peptide inhibits Langerhans cells antigen-presentin g function in several assays. Studies were performed to further explor e the hypothesis that Langerhans cells and nerves have a functional re lationship. To examine whether Langerhans cells may produce factors th at influence nerve cell differentiation, we utilized the Langerhans ce ll-like cell line XS52 as a surrogate for Langerhans cells and compare d it with Langerhans cells enriched to 90%. Supernatants conditioned b y lipopolysaccharide-stimulated XS52 cells were able to induce the dif ferentiation of the pheochromocytoma line PC12 into sympathetic neuron -like cells. This was also the case with enriched Langerhans cells sti mulated by lipopolysaccharide. Pre-treatment of conditioned supernatan ts with specific neutralizing anti-sera indicated that most of the dif ferentiation-inducing activity was due to interleukin-6 and a small am ount was due to nerve growth factor and basic fibroblast growth factor . By reverse transcriptase polymerase chain reaction, three clones of the XS52 cell line, XS52-4D, XS52-11D, and XS52-8B, were found to expr ess mRNA for interleukin-6 and expression was markedly augmented by li popolysaccharide. mRNA for nerve growth factor and basic fibroblast gr owth factor was detected in XS52-4D and XS52-11D, but not in XS52-8B. The expression of these neurotrophic factors by enriched Langerhans ce lls was quite similar to that of XS52-4D. In order to examine whether Langerhans cells may express receptors for nerve-derived peptides, rev erse transcriptase polymerase chain reaction was employed to look for pituitary adenylate cyclase activating polypeptide type I, type II, an d type III, and gastrin-releasing peptide receptors. All clones examin ed, as well as enriched Langerhans cells, expressed pituitary adenylat e cyclase activating polypeptide type II and type III, and gastrin-rel easing peptide receptors. These results suggest bi-directional signall ing between Langerhans cells and nerves; nerve cells may regulate Lang erhans cell function by elaboration of certain neuropeptides whereas L angerhans cells may promote the differentation of nerves by elaboratio n of interleukin-6 and, possibly, other factors.