Ruzicka T, Auböck J
J Immunol. 1987 Jan 15;138(2):539-43.
Epidermal Langerhans cells are macrophage-like la+ leukocytes that are critically involved in cutaneous immune reactions. Because macrophages exert their immunoregulatory activity in part by generation of oxygenated arachidonic acid metabolites, we systematically studied arachidonic acid transformations by purified guinea pig Langerhans cells and compared them with mixed epidermal cells and Langerhans cell-depleted keratinocytes. Products formed from arachidonic acid by cell homogenates were measured after thin-layer or reverse-phase high-pressure liquid chromatographic separation. In addition, leukotriene B4 and C4 formation was assessed in supernatants of Ca ionophore A23187-challenged intact cells by radioimmunoassay. Mixed epidermal cells converted arachidonic acid predominantly via cyclooxygenase and 12-lipoxygenase pathways. The main products were prostaglandin D2 (PGD2) and 12-hydroxyeicosatetraenoic acid (12-Hete), although significant amounts of PGE2, PGF2 alpha, and 6-keto-PGF1 alpha were formed as well. PGD2 synthesis was dependent on the presence of reduced glutathione. The product spectrum formed by Langerhans cell-depleted keratinocytes was virtually indistinguishable from mixed epidermal cells. In contrast, Langerhans cells showed a markedly different metabolism of arachidonic acid. They exhibited an exceedingly high PGD2-generating capacity, whereas only minor amounts of 12-HETE and very low amounts of other prostaglandins were synthesized. The PGD2/12-HETE ratio was 1.22 for mixed epidermal cells and 4.37 for Langerhans cells. Leukotriene production from exogenous or endogenous arachidonic acid could not be demonstrated by either radioenzymatic or radioimmunologic detection methods. We conclude that guinea pig Langerhans cells transform arachidonic acid predominantly to PGD2, which might mediate significant immunoregulatory, inflammatory, and antitumoral activity in the skin.
表皮朗格汉斯细胞是巨噬细胞样的la +白细胞，在皮肤免疫反应中起关键作用。由于巨噬细胞部分通过生成氧化型花生四烯酸代谢产物发挥其免疫调节活性，我们系统地研究了纯化的豚鼠朗格汉斯细胞对花生四烯酸的转化，并将其与混合表皮细胞和去除朗格汉斯细胞的角质形成细胞进行比较。在薄层或反相高压液相色谱分离后，测量细胞匀浆由花生四烯酸形成的产物。此外，通过放射免疫测定法评估钙离子载体A23187刺激的完整细胞上清液中白三烯B4和C4的形成。混合表皮细胞主要通过环氧化酶和12 -脂氧合酶途径转化花生四烯酸。主要产物是前列腺素D2（PGD2）和12 -羟基二十碳四烯酸（12 - Hete），尽管也形成了大量的PGE2、PGF2α和6 -酮 - PGF1α。PGD2的合成依赖于还原型谷胱甘肽的存在。去除朗格汉斯细胞的角质形成细胞形成的产物谱与混合表皮细胞几乎无法区分。相比之下，朗格汉斯细胞显示出明显不同的花生四烯酸代谢。它们表现出极高的PGD2生成能力，而仅合成少量的12 - HETE和极少量的其他前列腺素。混合表皮细胞的PGD2 / 12 - HETE比值为1.22，朗格汉斯细胞为4.37。通过放射酶法或放射免疫检测方法均未检测到外源性或内源性花生四烯酸产生白三烯。我们得出结论，豚鼠朗格汉斯细胞主要将花生四烯酸转化为PGD2，这可能在皮肤中介导重要的免疫调节、炎症和抗肿瘤活性。
