Nitric oxide-mediated depletion of Langerhans cells from the epidermis may be involved in UVA radiation-induced immunosuppression.
Ultraviolet A (UVA) irradiation of the dorsal skin of mice reduced the contact hypersensitivity (CHS) response and the density of epidermal Langerhans cells (LC). The roles of nitric oxide (NO) and reactive oxygen species (ROS) in these biological effects of UVA were investigated. Topical application of N(G)-monomethyl-L-arginine acetate, an inhibitor of NO production, 2,2'-dipyridyl, an iron chelater, or 4-hydroxy-tempo, a superoxide dismutase mimicking agent, inhibited UVA-induced suppression of the CHS response. N(G)-monomethyl-L-arginine acetate but not the ROS inhibitors prevented UVA from reducing LC numbers in the epidermis. This suggests that NO but not ROS produced in response to UVA mediates a depletion of LC from the epidermis, probably by signaling these cells to migrate from the skin. This could be responsible for UVA-induced immunosuppression. UVA-induced ROS can also cause immunosuppression, but by a different mechanism. Agents that inhibit or modulate NO or ROS production may be useful for preventing damage caused by the UVA component of sunlight to the skin immune system.
Yuen
Kylie S
KS
Department of Medicine, University of Sydney at Royal Prince Alfred Hospital, Sydney, New South Wales 2006, Australia.
Nearn
Malcolm R
MR
Halliday
Gary M
GM
D015082:2,2'-Dipyridyl / Q000494:pharmacology; D000818:Animals; D003497:Cyclic N-Oxides / Q000494:pharmacology; D000078404:Epidermal Cells; D004817:Epidermis / Q000528:radiation effects; D005260:Female; D007165:Immunosuppression Therapy; D007801:Langerhans Cells / Q000166:cytology*; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology*; D011837:Radiation-Protective Agents / Q000494:pharmacology; D013113:Spin Labels; D014466:Ultraviolet Rays; D019323:omega-N-Methylarginine / Q000494:pharmacology
D003497:Cyclic N-Oxides; D011837:Radiation-Protective Agents; D013113:Spin Labels; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D015082:2,2'-Dipyridyl; C001803:tempol