Monocytes enhance neutrophil-induced blister formation in an ex vivo model of bullous pemphigoid
Monocytes enhance neutrophil-induced blister formation in an ex vivo model of bullous pemphigoid
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DOI：
10.1111/all.13376
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发表时间：
2018-05-01
期刊：
影响因子：
12.4
通讯作者：
Simon, H. -U.
中科院分区：
文献类型：
--
作者：
de Graauw, E.;Sitaru, C.;Simon, H. -U.
背景大疱性类天疱疮（bullous pemphigoid，BP）是一种自身免疫性表皮下水疱性疾病，其特征是存在组织结合的和循环的抗半桥粒抗原的自身抗体，具有混合性炎性细胞浸润。在各种模型中，中性粒细胞、嗜酸性粒细胞、肥大细胞、单核细胞以及B和T细胞已被证明参与BP的发病机制。然而，它们与水疱形成的相互作用和有效作用仍然不确定。本研究的目的是调查的影响，单核细胞/中性粒细胞的相互作用对水泡形成在体外BP model.MethodsSkin cryosections与纯化的人中性粒细胞和单核细胞，在存在或不存在的BP自身抗体。使用适当的抑制剂研究活性氧（ROS）的产生、脱粒、介质释放（中性粒细胞弹性蛋白酶[NE]、髓过氧化物酶[MPO]、基质金属蛋白酶-9 [MMP-9]）、Fc受体（CD 16、CD 32、CD 64）的结合和细胞粘附（CD 18、ICAM-1）。真皮-表皮分离（DES）进行了评估，通过光学显微镜和定量Fiji software.ResultsMonocytes和中性粒细胞协同相互作用，导致显着更高的DES相比，无论是单核细胞或中性粒细胞分别（P < .0001）。单核细胞/嗜酸性粒细胞诱导的DES与增加的ROS产生相关，并且依赖于粘附和FcRIII结合。在刺激的粒-贫部分的单核细胞上清液，中性粒细胞增加了他们的MMP-9的释放，从而也DES在真皮-表皮交界处的皮肤cryosecies.ConclusionOur的观察表明，细胞的相互作用，如这里所示的单核细胞和中性粒细胞，增强介体释放导致增加皮下水疱形成。因此，阻断细胞间串扰有望成为阻断BP组织损伤的新治疗方法。
BackgroundLesions of bullous pemphigoid (BP), an autoimmune subepidermal blistering disease characterized by the presence of tissue-bound and circulating autoantibodies to hemidesmosomal antigens, harbor a mixed inflammatory cellular infiltrate. In various models, neutrophils, eosinophils, mast cells, monocytes as well as B and T cells have been shown to be involved in the pathogenesis of BP. However, their interactions with and effective role in blister formation remain uncertain. This study was aimed at investigating the effect of monocyte/neutrophil interaction on blister formation in an ex vivo BP model.MethodsSkin cryosections were incubated with purified human neutrophils and monocytes, in the presence or absence of BP autoantibodies. Production of reactive oxygen species (ROS), degranulation, mediator release (neutrophil elastase [NE], myeloperoxidase [MPO], matrix metalloproteinase-9 [MMP-9]), binding of Fc receptor (CD16, CD32, CD64), and cell adhesion (CD18, ICAM-1) was investigated using appropriate inhibitors. Dermal-epidermal separation (DES) was assessed by light microscopy and quantified by Fiji software.ResultsMonocytes and neutrophils synergistically interact resulting in a significantly higher DES compared to either monocytes or neutrophils separately (P < .0001). Monocyte/neutrophil-induced DES was associated with increased ROS production and was dependent on adhesion and FcRIII binding. Upon stimulation by the granule-poor fraction of monocyte supernatants, neutrophils increased their release of MMP-9, thereby also DES at the dermal-epidermal junction of skin cryosections.ConclusionOur observations suggest that the interaction of cells, as shown here for monocytes and neutrophils, enhances mediator release resulting in an increased subepidermal blister formation. Thus, blocking intercellular cross talk promises a new therapeutic approach for blocking tissue damage in BP.