Nicotinic acid-induced flushing is mediated by activation of epidermal langerhans cells
Nicotinic acid-induced flushing is mediated by activation of epidermal langerhans cells
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DOI：
10.1124/mol.106.030833
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发表时间：
2006-12-01
影响因子：
3.6
通讯作者：
Offermanns, Stefan
中科院分区：
文献类型：
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作者：
Benyo, Zoltan;Gille, Andreas;Offermanns, Stefan
降血脂药物烟酸(烟酸)已经使用了几十年。烟酸治疗使用的主要问题之一是一种强烈的皮肤血管扩张，称为潮红，几乎在每个服用烟酸的患者中都会发生这种情况。烟酸诱导的潮红已被证明是由烟酸受体Gpr109a介导的，并涉及血管扩张性前列腺素的形成。然而，这种短期效应背后的细胞机制尚不清楚。在这里，我们证明了表皮朗格汉斯细胞对于烟酸引起的皮肤潮红反应是必不可少的。朗格汉斯细胞对烟酸的反应是[Ca~(2+)](I)升高，并表达前列腺素合成酶，这是血管扩张前列腺素E-2和前列腺素D-2形成所必需的。去除表皮朗格汉斯细胞而不是巨噬细胞或树突状细胞可以消除烟酸引起的潮红。这些数据出人意料地将表皮朗格汉斯细胞确定为烟酸诱导潮红的基本媒介，并可能有助于制定新的策略来抑制烟酸的有害影响。此外，我们的结果表明，郎格汉斯细胞除了在免疫学上的作用外，还参与了真皮血流的局部调节。
The antidyslipidemic drug nicotinic acid (niacin) has been used for decades. One of the major problems of the therapeutical use of nicotinic acid is a strong cutaneous vasodilation called flushing, which develops in almost every patient taking nicotinic acid. Nicotinic acid-induced flushing has been shown to be mediated by the nicotinic acid receptor GPR109A and to involve the formation of vasodilatory prostanoids. However, the cellular mechanisms underlying this short-term effect are unknown. Here, we show that epidermal Langerhans cells are essential for the cutaneous flushing response induced by nicotinic acid. Langerhans cells respond with an increase in [Ca2+](i) to nicotinic acid and express prostanoid synthases required for the formation of the vasodilatory prostanoids prostaglandin E-2 and prostaglandin D-2. Depletion of epidermal Langerhans cells but not of macrophages or dendritic cells abrogates nicotinic acid-induced flushing. These data unexpectedly identify epidermal Langerhans cells as essential mediators of nicotinic acid-induced flushing and may help to generate new strategies to suppress the unwanted effects of nicotinic acid. In addition, our results suggest that Langerhans cells besides their immunological roles are also involved in the local regulation of dermal blood flow.