Local ultraviolet B irradiation impairs contact hypersensitivity inductionby triggering release of tumor necrosis factor-alpha from mast cells. Involvement of mast cells and Langerhans cells in susceptibility to ultravioletB

Our laboratory has previously demonstrated that ultraviolet B radiation imp airs contact hypersensitivity induction in ultraviolet B susceptible mice t hrough a tumor necrosis factor-alpha-dependent mechanism, involving calcito nin 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 ultraviolet B-susceptible phenotype, As dermal m ast cells seem to release tumor necrosis factor-alpha following exposure to ultraviolet B, we investigated whether tumor necrosis factor-alpha release d by mast cells could mediate impairment of contact hypersensitivity in a m anner similar to that found with ultraviolet B radiation treatment. First, we loaded Fc epsilon receptors of mast cells of ultraviolet B-susceptible ( C3H/HeN), ultraviolet B-resistant (C3H/HeJ), and mast-cell deficient (Sl/Sl (d)) mice by intradermal injections of anti-dinitrophenyl immunoglobulin E antibodies. Twenty-four hours later, dinitrophenyl was injected intravenous ly, 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/Sl(d) mice, and treatment with an ti-tumor necrosis factor-alpha antibodies was able to reverse this impairme nt of contact hypersensitivity. Second, we have found that ultraviolet B ra diation did not impair contact hypersensitivity induction when haptens were painted on irradiated skin of mast cell deficient mice. As ultraviolet B r adiation impairs contact hypersensitivity induction through a tumor necrosi s factor-alpha-dependent mechanism, we conclude that ultraviolet B radiatio n triggers the prompt release of tumor necrosis factor-alpha from dermal ma st cells, and that mast cell-derived tumor necrosis factor-alpha interferes with generation of the hapten-specific signal required for contact hyperse nsitivity induction. In addition, we are providing data that indicate that tumor necrosis factor-alpha levels released from mast cells as well as sens itivity of Langerhans cells to tumor necrosis factor-alpha contribute in de fining the phenotypes of resistance versus sensitivity to ultraviolet B rad iation.