Nitric oxide appears to be a mediator of solar-simulated ultraviolet radiation-induced immunosuppression in humans.
Topical application of NG-methyl-L-arginine and 2,2'-dipyridyl were used to examine the respective roles of nitric oxide and reactive oxygen species in solar-simulated ultraviolet radiation-induced immunosuppression in humans in vivo. Immunosuppression was studied using a nickel contact hypersensitivity recall model. Ultraviolet radiation dose-responses were generated to determine the extent to which NG-methyl-L-arginine and 2,2'-dipyridyl affected the immune response. NG-methyl-L-arginine but not 2,2'-dipyridyl protected the immune system from ultraviolet radiation-induced suppression. Both NG-methyl-L-arginine and 2,2'-dipyridyl inhibited nitrite production. Nitrite is a degradation product of peroxynitrite, a cytotoxic mediator resulting from reactions between nitric oxide and reactive oxygen species. This suggests that nitric oxide, not its downstream product peroxynitrite, was likely to be responsible for solar-simulated ultraviolet radiation-induced immunosuppression. In contrast, both nitric oxide and reactive oxygen species were mediators of solar-simulated ultraviolet radiation-induced apoptosis and loss of dendritic S-100+ cells (probably Langerhans cells) from the epidermis. It is likely that different mechanisms are involved in these ultraviolet-induced endpoints and that events in addition to Langerhans cell depletion are important for local immune suppression to recall antigens in humans. Understanding the mechanisms of cutaneous ultraviolet-induced oxidative stress will assist in the future design of novel products that protect skin from photoaging and skin cancer.
Kuchel
Johanna M
JM
Department of Medicine (Dermatology), The Melanoma and Skin Cancer Research Institute, Royal Prince Alfred Hospital at The University of Sydney, Sydney, NSW 2006, Australia.
Barnetson
Ross St C
RS
Halliday
Gary M
GM
D015082:2,2'-Dipyridyl / Q000494:pharmacology; D000328:Adult; D017209:Apoptosis / Q000528:radiation effects; D003877:Dermatitis, Contact / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy; D007202:Indicators and Reagents / Q000494:pharmacology; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D009532:Nickel; D009569:Nitric Oxide / Q000378:metabolism*; D010328:Patch Tests; D017382:Reactive Oxygen Species / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D013471:Sunburn / Q000276:immunology; D013472:Sunlight / Q000009:adverse effects; D014466:Ultraviolet Rays / Q000009:adverse effects*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D005609:Free Radicals; D007202:Indicators and Reagents; D017382:Reactive Oxygen Species; D009418:S100 Proteins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D015082:2,2'-Dipyridyl; D009532:Nickel