Calcitonin gene-related peptide is necessary for ultraviolet B-impaired induction of contact hypersensitivity.
Since nerve termini on Langerhans cells (LC) contain calcitonin gene-related peptide (CGRP), and since ultraviolet B radiation (UVR) causes CGRP to be released from cutaneous nerve endings, we examined whether CGRP participates in the immune aberrations caused in skin by UVR. First, intradermally injected CGRP, in a dose-dependent manner, reduced LC density and impaired CH induction when hapten was painted on the injected site. Second, CGRP antagonist restored CH induction after UVR. Third, anti-TNF-alpha Abs injected before CGRP prevented the loss of LC density and restored CH induction. Fourth, CGRP failed to impair CH induction in mast cell-deficient mice. Fifth, CGRP induced mast cells to release TNF-alpha. We conclude that CGRP plays an essential role in the loss of CH induction after UVR. These data indicate that UVR, by causing the release of CGRP from cutaneous nerve endings, triggers mast cell release of TNF-alpha, which impairs CH induction.
Niizeki
H
H
Schepens Eye Research Institute and Department of Dermatology, Harvard Medical School, Boston, MA 02114, USA.
Alard
P
P
Streilein
J W
JW
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D003877:Dermatitis, Contact / Q000209:etiology*; D004139:Dinitrofluorobenzene; D004305:Dose-Response Relationship, Drug; D007801:Langerhans Cells / Q000378:metabolism* / Q000528:radiation effects*; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D012867:Skin / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D014466:Ultraviolet Rays
D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha; D004139:Dinitrofluorobenzene; D015740:Calcitonin Gene-Related Peptide