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, calcitonin gene-related peptide inhibits Langerhans cells antigen-presenting function in several assays. Studies were performed to further explore the hypothesis that Langerhans cells and nerves have a functional relationship. To examine whether Langerhans cells may produce factors that influence nerve cell differentiation, we utilized the Langerhans cell-like cell line XS52 as a surrogate for Langerhans cells and compared it with Langerhans cells enriched to 90%. Supernatants conditioned by lipopolysaccharide-stimulated XS52 cells were able to induce the differentiation of the pheochromocytoma line PC12 into sympathetic neuron-like cells. This was also the case with enriched Langerhans cells stimulated by lipopolysaccharide. Pretreatment of conditioned supernatants with specific neutralizing anti-sera indicated that most of the differentiation-inducing activity was due to interleukin-6 and a small amount 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 express mRNA for interleukin-6 and expression was markedly augmented by lipopolysaccharide. mRNA for nerve growth factor and basic fibroblast growth factor was detected in XS52-4D and XS52-11D, but not in XS52-8B. The expression of these neurotrophic factors by enriched Langerhans cells was quite similar to that of XS52-4D. In order to examine whether Langerhans cells may express receptors for nerve-derived peptides, reverse transcriptase polymerase chain reaction was employed to look for pituitary adenylate cyclase activating polypeptide type I, type II, and type III, and gastrin-releasing peptide receptors. All clones examined, as well as enriched Langerhans cells, expressed pituitary adenylate cyclase activating polypeptide type II and type III, and gastrin-releasing peptide receptors. These results suggest bi-directional signalling between Langerhans cells and nerves; nerve cells may regulate Langerhans cell function by elaboration of certain neuropeptides whereas Langerhans cells may promote the differentation of nerves by elaboration of interleukin-6 and, possibly, other factors.
Torii
H
H
Department of Dermatology, Cornell University Medical College, New York, NY 10021, U.S.A.
Yan
Z
Z
Hosoi
J
J
Granstein
R D
RD
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D004817:Epidermis / Q000294:innervation; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000276:immunology; D007106:Immune Sera / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007801:Langerhans Cells / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009414:Nerve Growth Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009424:Nervous System Physiological Phenomena; D009433:Neural Inhibition; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D016716:PC12 Cells / Q000473:pathology / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018013:Receptors, Neuropeptide / Q000378:metabolism*
D007106:Immune Sera; D015850:Interleukin-6; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D018013:Receptors, Neuropeptide; D016222:Fibroblast Growth Factor 2