Local ultraviolet B irradiation impairs contact hypersensitivity induction by triggering release of tumor necrosis factor-alpha from mast cells. Involvement of mast cells and Langerhans cells in susceptibility to ultraviolet B.
Our laboratory has previously demonstrated that ultraviolet B radiation impairs contact hypersensitivity induction in ultraviolet B susceptible mice through a tumor necrosis factor-alpha-dependent mechanism, involving calcitonin gene related peptide and cutaneous mast cells. This study was designed to test directly whether mast cells are the source of tumor necrosis factor-alpha, to account for the ultra-violet B-susceptible phenotype. As dermal mast cells seem to release tumor necrosis factor-alpha following exposure to ultraviolet B, we investigated whether tumor necrosis factor-alpha released by mast cells could mediate impairment of contact hypersensitivity in a manner similar to that found with ultraviolet B radiation treatment. First, we loaded Fcepsilon receptors of mast cells of ultraviolet B-susceptible (C3H/HeN), ultraviolet B-resistant (C3H/HeJ), and mast-cell deficient (Sl/Sld) mice by intradermal injections of anti-dinitrophenyl immunoglobulin E antibodies. Twenty-four hours later, dinitrophenyl was injected intravenously, and within 30 min oxazolone was painted on injected skin sites. Contact hypersensitivity induction was impaired in ultraviolet B-susceptible mice, but not in ultraviolet B-resistant or Sl/Sld mice, and treatment with anti-tumor necrosis factor-alpha antibodies was able to reverse this impairment of contact hypersensitivity. Second, we have found that ultraviolet B radiation did not impair contact hypersensitivity induction when haptens were painted on irradiated skin of mast cell deficient mice. As ultraviolet B radiation impairs contact hypersensitivity induction through a tumor necrosis factor-alpha-dependent mechanism, we conclude that ultraviolet B radiation triggers the prompt release of tumor necrosis factor-alpha from dermal mast cells, and that mast cell-derived tumor necrosis factor-alpha interferes with generation of the hapten-specific signal required for contact hypersensitivity induction. In addition, we are providing data that indicate that tumor necrosis factor-alpha levels released from mast cells as well as sensitivity of Langerhans cells to tumor necrosis factor-alpha contribute in defining the phenotypes of resistance versus sensitivity to ultra-violet B radiation.
Alard
P
P
Schepens Eye Research Institute, Department of Dermatology, Harvard Medical School, Boston, MA 02114, USA.
Niizeki
H
H
Hanninen
L
L
Streilein
J W
JW
D000818:Animals; D015550:Cell Degranulation; D003877:Dermatitis, Contact / Q000517:prevention & control*; D007073:Immunoglobulin E / Q000276:immunology; D007801:Langerhans Cells / Q000502:physiology*; D008407:Mast Cells / Q000502:physiology / Q000528:radiation effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011836:Radiation Tolerance; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E