Identification of the molecular target for the suppression of contact hypersensitivity by ultraviolet radiation.
Identification of the molecular target for the suppression of contact hypersensitivity by ultraviolet radiation.
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DOI：
10.1084/jem.170.4.1117
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发表时间：
1989-10-01
期刊：
影响因子：
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通讯作者：
Kripke ML
中科院分区：
文献类型：
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作者：
Applegate LA;Ley RD;Alcalay J;Kripke ML
本研究旨在探讨DNA损伤在紫外线照射抑制接触性超敏反应(CHS)中的作用。之所以使用负鼠，是因为这些有袋类动物的细胞有一种酶，可以被可见光激活(光复活酶)，并修复紫外线辐射(UVR)诱导的DNA中的嘧啶二聚体。对负鼠背部皮肤进行单次剂量为1500 J/m2(280-320 nm)的UVB辐射，相当于2个最小红斑剂量。这种处理防止了负鼠对照射部位或未照射部位施加的二硝基氟苯(DNFB)产生CHS反应。此外，在使用DNFB时，该剂量的UVR使背侧表皮中的ATPase+表皮朗格汉斯细胞的数量减少到未照射皮肤的约3%。紫外光照射后立即用激活修复酶的波长(320-500 nm，光复活光，PRL)处理120分钟，几乎完全抑制UVR诱导的CHS抑制。UVR前暴露于PRL并不能阻止UVR诱导的CHS抑制。紫外线照射后的PRL处理也能阻止ATPase+朗格汉斯细胞数量的减少。DNA损伤的测量表明，PRL处理去除了大约85%的UVR诱导的嘧啶二聚体。这些数据提供了直接的证据，证明DNA，最有可能的是嘧啶二聚体，是UVB诱导的抑制对辐射或未暴露的皮肤的半抗原接触过敏的主要分子靶标。
This study was conducted to explore the involvement of DNA damage in the suppression of contact hypersensitivity (CHS) by UV irradiation. The opossum, Monodelphis domestica, was used because cells of these marsupials have an enzyme that is activated by visible light (photoreactivating enzyme) and repairs ultraviolet radiation (UVR)- induced pyrimidine dimers in DNA. A single dose of 1,500 J/m2 of UVB (280-320 nm) radiation, representing 2 minimal erythema doses, was administered to the dorsal skin of opossums. This treatment prevented the opossums from developing a CHS response to dinitrofluorobenze (DNFB) applied either at the site of irradiation or an unirradiated site. In addition, this dose of UVR decreased the number of ATPase+ epidermal Langerhans cells in the dorsal epidermis to approximately 3% of that in unirradiated skin at the time of DNFB application. Treatment of the animals with wavelengths that activate the repair enzyme (320- 500 nm, photoreactivating light, PRL) for 120 min immediately after UV irradiation inhibited the UVR-induced suppression of CHS almost completely. Exposure to PRL before UVR did not prevent UVR-induced suppression of CHS. PRL treatment after UV irradiation also prevented the decrease in the number of ATPase+ Langerhans cells. Measurements of lesions in DNA indicated that PRL treatment removed around 85% of the UVR-induced pyrimidine dimers. These data provide direct evidence that DNA, and most likely, the pyrimidine dimer, is the primary molecular target for the UVB-induced suppression of contact hypersensitivity to haptens applied to irradiated or unexposed skin.