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首页> 外文期刊>The Journal of investigative dermatology. >The Leukotriene B-4 and its Receptor BLT1 Act as Critical Drivers of Neutrophil Recruitment in Murine Bullous Pemphigoid-Like Epidermolysis Bullosa Acquisita
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The Leukotriene B-4 and its Receptor BLT1 Act as Critical Drivers of Neutrophil Recruitment in Murine Bullous Pemphigoid-Like Epidermolysis Bullosa Acquisita

机译：白三烯B-4及其受体BLT1充当小鼠大疱性Pemphigoide表皮细胞Bullosa Acquisita的中性粒细胞募集的关键司机

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Recruitment of neutrophils and eosinophils into the skin is a hallmark of pemphigoid diseases. The molecular cues regulating granulocyte recruitment into the skin and the individual contributions of neutrophils and eosinophils to pemphigoid diseases are, however, poorly understood. The lipid mediator leukotriene B-4 (LTB4) is a potent granulocyte chemoattractant and is abundant in the skin blister fluid of bullous pemphigoid (BP) patients, but its pathogenic significance is unknown. Using mouse models of BP-like epidermolysis bullosa acquisita and of BP, we show that LTB4 and its receptor BLT1 act as critical drivers of neutrophil entry into the skin upon antibody deposition at the dermal-epidermal junction. Mice deficient in 5-lipoxygenase, a key enzyme in LTB4 biosynthesis, or in BLT1 exhibited dramatic resistance to neutrophil recruitment and, consequently, skin inflammation. Accordingly, liquid chromatography-mass spectrometry, used to comprehensively profile lipid mediator generation in the first 48 hours after antibody deposition, showed a pronounced parallel increase in LTB4 and in neutrophils in the skin. Subsequent mechanistic studies in BP-like epidermolysis bullosa acquisita uncovered that neutrophils are necessary for skin inflammation, whereas eosinophils are dispensable, thus identifying neutrophils as major culprits of blister formation. Our results highlight LTB4/BLT1 as absolutely critical drivers of murine pemphigoid disease-like skin inflammation.
机译：患有中性粒细胞和嗜酸性粒细胞的募集到皮肤上是一种毒性疾病的标志。然而，调节粒细胞募集到皮肤中的分子提示以及中性粒细胞和嗜酸性粒细胞对发汗疾病的个体贡献是较差的。脂质介导白酮B-4（LTB4）是一种有效的粒细胞化学趋化剂，并且在大疱性疱疹（BP）患者的皮肤泡沫流体中丰富，但其致病性意义是未知的。使用BP样表皮细胞Bullosa acciSita和BP的小鼠模型，我们表明LTB4及其受体BLT1作为在皮肤表皮结处的抗体沉积时作为中性粒细胞进入皮肤的关键驱动器。缺乏5-脂氧合酶的小鼠，LTB4生物合成中的关键酶，或在BLT1中表现出对中性粒细胞募集的显着抗性，并且因此皮肤炎症。因此，液相色谱 - 质谱法用于在抗体沉积后的前48小时内全面突出脂质介质，在皮肤上的LTB4和中性粒细胞中显示出明显的平行增加。随后的BP样表皮分解Bullosa Arbisita揭示中性粒细胞对于皮肤炎症是必需的，而嗜酸性粒细胞是可分配的，因此将嗜中性粒细胞鉴定为泡罩形成的主要罪魁祸首。我们的结果突出了LTB4 / BLT1作为鼠鼠蝇状疾病的绝对关键驱动因素样疾病样皮肤炎症。

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