Ultraviolet B radiation generates platelet-activating factor-like phospholipids underlying cutaneous damage
Ultraviolet B radiation generates platelet-activating factor-like phospholipids underlying cutaneous damage
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DOI：
10.1074/jbc.m503811200
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发表时间：
2005-10-21
影响因子：
4.8
通讯作者：
Travers, JB
中科院分区：
文献类型：
--
作者：
Marathe, GK;Johnson, C;Travers, JB
紫外线B光（UVB）引起皮肤炎症和细胞死亡，但负责的因素尚未确定。这些研究探讨了血小板活化因子（PAF）信号系统在UVB介导效应中的作用。UVB照射下PAF受体阴性表皮样细胞KB中PAF受体的表达增强了细胞凋亡。在体外实验中，原代人角质形成细胞中过表达PAF受体也增强了UVB介导的细胞凋亡，在移植到严重联合免疫缺陷（SCID）小鼠体内模型中，PAF受体增强了人角质形成细胞的凋亡。为了确定UVB激活PAF受体的机制，我们使用质谱法证明了在UVB照射后表皮细胞系中大量的C-4 PAF类似物1-烷基- 2（丁烷酰和丁烯酰）- sn-甘油- 3-磷酸胆碱以及天然PAF。用前体磷脂1-十六烷基- 2-花生四烯醇基- sn-甘油- 3-磷酸胆碱（HAPC）补充细胞增加了UVB暴露后回收的C-4 PAF类似物的数量。我们直接照射HAPC，发现即使在没有光敏剂的情况下，它也会分裂成C-4- PAF受体配体。我们得出结论，UVB光氧化细胞磷脂，产生PAF类似物，刺激PAF受体，进一步诱导PAF合成和凋亡。PAF信号可能参与在光加重性皮肤病中发生的皮肤炎症。
Ultraviolet B light ( UVB) causes cutaneous inflammation and cell death, but the agents responsible are not defined. These studies examined the role of the platelet- activating factor ( PAF) signaling system in UVB- mediated effects. Expression of the PAF receptor in the PAF receptor- negative epidermoid cell line KB augmented apoptosis in response to UVB irradiation. Overexpression of the PAF receptor in primary human keratinocytes also enhanced UVB- mediated apoptosis in vitro, and it enhanced apoptosis in an in vivo model of human keratinocytes grafted onto severe combined immune- deficient ( SCID) mice. To define the mechanism by which UVB activates the PAF receptor, we used mass spectrometry to demonstrate significant amounts of the C-4 PAF analogs 1- alkyl- 2( butanoyl and butenoyl)- sn- glycero- 3- phosphocholine, as well as native PAF in an epidermal cell line after UVB irradiation. Supplementing the cells with the precursor phospholipid 1- hexadecyl- 2-arachidonoyl- sn- glycero- 3- phosphocholine ( HAPC) increased the amount of C-4 PAF analogs recovered after UVB exposure. We irradiated HAPC directly and found, even in the absence of a photosensitizer, fragmentation to C-4- PAF receptor ligands. We conclude UVB photo- oxidizes cellular phospholipids, creating PAF analogs that stimulate the PAF receptor to induce further PAF synthesis and apoptosis. PAF signaling may participate in the cutaneous inflammation that occurs during photo- aggravated dermatoses.