EPIDERMIS CONTAINS PLATELET-TYPE 12-LIPOXYGENASE THAT IS OVEREXPRESSED IN GERMINAL LAYER KERATINOCYTES IN PSORIASIS
EPIDERMIS CONTAINS PLATELET-TYPE 12-LIPOXYGENASE THAT IS OVEREXPRESSED IN GERMINAL LAYER KERATINOCYTES IN PSORIASIS
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DOI：
10.1152/ajpcell.1994.266.1.c243
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发表时间：
1994-01-01
影响因子：
--
通讯作者：
HOLTZMAN, MJ
中科院分区：
文献类型：
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作者：
HUSSAIN, H;SHORNICK, LP;HOLTZMAN, MJ
人表皮细胞没有表现出在粘膜上皮细胞中突出的胞质脂氧合酶活性，而是含有将花生四烯酸转化为12-羟基二十碳四烯酸（12-HETE）的微粒体活性。作为12-脂氧合酶（与细胞色素P-450不同）的可提取12-HETE形成活性的鉴定包括产物形成的（S）-12-立体特异性、捕获作为中间反应产物的12-氢过氧二十碳四烯酸以及活性不依赖于NADPH。表皮细胞poly（A）（+）RNA中含有高水平的2.3kb的mRNA，该mRNA可与人血小板12-脂氧合酶cDNA选择性杂交，其部分cDNA序列表明与血小板1a-脂氧合酶相同。表皮12-脂氧合酶不被白细胞型12-和15-脂氧合酶（发现于白细胞，网织红细胞和粘膜上皮细胞）的抗体识别，但被检测到的抗血小板Ia-脂氧合酶抗体。表皮12-脂氧合酶抗原选择性地表达在健康和银屑病皮肤的生发层角质形成细胞，这些层表现出增生和银屑病皮肤炎症免疫染色增加。与以前的结果一起，这些观察结果表明：1）表皮通过细胞色素P-450或脂氧合酶的机制产生12-HETE，这取决于反应条件，和2）12-脂氧合酶（最初在造血细胞类型中描述）可以在人类上皮屏障中以至少两种不同的同种型表达，并且在皮肤的情况下，微粒体（血小板型）12-脂氧合酶在银屑病炎症期间在表皮层角质形成细胞中选择性过表达。
Human epidermal cells exhibited none of the cytosolic lipoxygenase activity that is prominent in mucosal epithelial cells, but instead contained a microsomal activity that converted arachidonic acid to 12-hydroxyeicosatetraenoic acid (12-HETE). Identification of the extractable 12-HETE-forming activity as a 12-lipoxygenase (distinct from cytochrome P-450) included (S)-12-stereospecificity of product formation, trapping of 12-hydroperoxyeicosatetraneoic acid as an intermediate reaction product, and lack of NADPH dependence for activity. Epidermal cell poly(A)(+) RNA contained high levels of a 2.3-kb mRNA that selectively hybridized with human platelet 12-lipoxygenase cDNA, and partial cDNA sequence of this mRNA indicated identity to platelet la-lipoxygenase. The epidermal 12-lipoxygenase was not recognized by antibodies against the leukocyte-type 12- and 15-lipoxygenases (found in leukocytes, reticulocytes, and mucosal epithelial cells) but was detected by an antiplatelet la-lipoxygenase antibody. The epidermal 12-lipoxygenase antigen was selectively expressed in germinal layer keratinocytes in healthy and psoriatic skin, and these layers exhibited hyperplasia and increased immunostaining in inflamed psoriatic skin. Together with previous results, these observations indicate that 1) epidermis generates 12-HETE by either cytochrome P-450- or lipoxygenase-based mechanisms depending on reaction conditions, and 2) 12-lipoxygenases (originally described in hematopoietic cell types) may be expressed in at least two distinct isoforms in epithelial barriers in humans, and in the case of the skin, a microsomal (platelet-type) 12-lipoxygenase is selectively overexpressed in germinal layer keratinocytes during psoriatic inflammation.