Reeve V E, Tyrrell R M
Department of Veterinary Anatomy and Pathology, University of Sydney, N.S.W. 2006, Sydney, Australia.
Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9317-21. doi: 10.1073/pnas.96.16.9317.
In contrast to the immunosuppressive potential of UVB (280-320 nm) radiation in experimental animals and humans, UVA (320-400 nm) radiation at environmentally relevant doses appears to be immunologically inert. However, such exposure to UVA radiation has been observed unexpectedly to induce resistance to UVB-induced immunosuppression in mice, by a mechanism resulting in the inactivation of cis-urocanic acid (UCA), an epidermal immunosuppressive UV photoproduct. In this study in mice, we show that the immunoprotective activity of UVA radiation, against the effects of both UVB radiation and cis-UCA, can be attributed to the induction of cutaneous heme oxygenase (HO; EC 1.14.99.3). Cell-mediated immune function was assessed in vivo by the contact hypersensitivity response induced to oxazolone at an unirradiated skin site, and HO enzyme activity was measured in cutaneous microsomal preparations from treated mice. There was a progressive increase in HO enzyme activity for at least 3 days after UVA irradiation. However HO activity, both constitutive and UVA radiation-induced, was sensitive to the effects of injecting mice with the specific HO inhibitor, tin protoporphyrin (Sn [IV] protoporphyrin IX; SnPP). We observed, in addition, that in SnPP-injected mice, the immunoprotective effect of UVA radiation against either UVB radiation or cis-UCA was abrogated. Because SnPP injection did not affect normal contact hypersensitivity responsiveness but did inhibit the constitutive HO enzyme activity, it appeared that only the inducible HO was active in modulating immune function. This finding indicates that UVA-induced HO activity is a major player in the skin defenses against UVB immunosuppression.
与紫外线B（280 - 320纳米）辐射在实验动物和人类中的免疫抑制潜力相反，环境相关剂量的紫外线A（320 - 400纳米）辐射在免疫学上似乎是惰性的。然而，意外观察到，这种紫外线A辐射暴露可通过一种导致顺式尿刊酸（UCA）失活的机制，诱导小鼠对紫外线B诱导的免疫抑制产生抗性，UCA是一种表皮免疫抑制性紫外线光产物。在这项小鼠研究中，我们表明，紫外线A辐射针对紫外线B辐射和顺式UCA的免疫保护活性可归因于皮肤血红素加氧酶（HO；EC 1.14.99.3）的诱导。通过在未照射皮肤部位对恶唑酮诱导的接触性超敏反应在体内评估细胞介导的免疫功能，并在处理小鼠的皮肤微粒体制剂中测量HO酶活性。紫外线A照射后至少3天，HO酶活性逐渐增加。然而，组成型和紫外线A辐射诱导的HO活性对给小鼠注射特异性HO抑制剂锡原卟啉（Sn[IV]原卟啉IX；SnPP）的影响敏感。此外，我们观察到，在注射SnPP的小鼠中，紫外线A辐射对紫外线B辐射或顺式UCA的免疫保护作用被消除。因为注射SnPP不影响正常的接触性超敏反应性，但确实抑制组成型HO酶活性，似乎只有诱导型HO在调节免疫功能中起作用。这一发现表明，紫外线A诱导的HO活性是皮肤抵御紫外线B免疫抑制的主要因素。
