Interactions of eosinophil granule proteins with skin: Limits of detection, persistence, and vasopermeabilization
Interactions of eosinophil granule proteins with skin: Limits of detection, persistence, and vasopermeabilization
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DOI：
10.1016/j.jaci.2003.08.028
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发表时间：
2003-11-01
影响因子：
14.2
通讯作者：
Leiferman, KM
中科院分区：
文献类型：
--
作者：
Davis, MDP;Plager, DA;Leiferman, KM
背景资料：嗜酸性粒细胞颗粒蛋白，包括嗜酸性粒细胞阳离子蛋白（ECP）、嗜酸性粒细胞衍生的神经毒素（EDN）、嗜酸性粒细胞过氧化物酶（EPO）和主要碱性蛋白（MBP），在多种皮肤疾病中显著沉积在皮肤中，并可能与疾病病理学有关。目的：我们试图确定皮肤中嗜酸性粒细胞颗粒蛋白的检测限、持久性和血管通透性活性。皮内注射嗜酸性粒细胞颗粒蛋白。用间接免疫荧光法测定了它们在人体外科废弃皮肤中的最低检出浓度和在豚鼠皮肤中的持久性。结果：经皮最低检测浓度分别为0.05 μ mol/L EPO、0.1 μ mol/L MBP、0.25 μ mol/L ECP和1 μ mol/L EDN。颗粒蛋白在体内豚鼠皮肤中持续1周（EPO）、2周（ECP）、2.5周（EDN）和6周（MBP）。每种嗜酸性粒细胞颗粒蛋白以浓度依赖性方式增加皮肤血管通透性。每种颗粒蛋白诱导的血管通透性的效力与组胺相当。马来酸吡拉明预处理的豚鼠并没有改变ECP和EDN诱导的血管通透性增加，但显着抑制诱导EPO和MBP.Conclusions：微摩尔浓度的嗜酸性粒细胞颗粒蛋白往往沉积在皮肤嗜酸性粒细胞相关的皮肤疾病，如特应性皮炎。这些嗜酸性粒细胞颗粒蛋白的病理生理相关浓度导致皮肤血管通透性增加（通过组胺非依赖性和组胺依赖性机制），并可能改变皮肤功能数天至数周。
Background: Eosinophil granule proteins, including eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), eosinophil peroxidase (EPO), and major basic protein (MBP), are prominently deposited in skin in several cutaneous disorders and likely contribute to disease pathology.Objective: We sought to determine the limit of detection, persistence, and vasopermeabilization activity of the eosinophil granule proteins in skin.Methods: The eosinophil granule proteins were injected intradermally. Their minimum detectable concentrations in human surgical waste skin and their persistence in guinea pig skin were determined by indirect immunofluorescence. Vasopermeabilization activity in the guinea pig without and with H-1 antihistamine (pyrilamine maleate) pretreatment was assessed by extrusion of Evans blue dye-treated plasma.Results: The lowest detectable cutaneous concentrations were 0.05 mumol/L EPO, 0.1 mumol/L MBP, 0.25 mumol/L ECP, and 1 mumol/L EDN. Granule proteins persisted in guinea pig skin in vivo for 1 week (EPO), 2 weeks (ECP), 2.5 weeks (EDN), and 6 weeks (MBP). Each of the eosinophil granule proteins increased cutaneous vasopermeability in a concentration-dependent manner. The potency of vasopermeabilization induced by each granule protein was comparable with that of histamine. Pyrilamine maleate pretreatment of guinea pigs did not alter increased vasopermeability induced by ECP and EDN but significantly inhibited that induced by EPO and MBP.Conclusions: Micromolar concentrations of eosinophil granule proteins are often deposited in skin in eosinophil-associated cutaneous disorders such as atopic dermatitis. These patho-physiologically relevant concentrations of eosinophil granule proteins cause increased cutaneous vasopermeability (both by means of histamine-independent and histamine-dependent mechanisms) and might alter cutaneous function for days to weeks.