肥大细胞在金黄色葡萄球菌肠毒素B诱导小鼠特应性皮炎样炎症反应中的作用

王珊; 赵作涛; 王誉涵; 涂平; 刘玲玲

doi:10.3760/cma.j.issn.0412-4030.2018.01.007

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中华皮肤科杂志

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ENGLISH ABSTRACT

肥大细胞在金黄色葡萄球菌肠毒素B诱导小鼠特应性皮炎样炎症反应中的作用

作者及单位信息

出版日期： 2018 -01 -15 ·

DOI： 10.3760/cma.j.issn.0412-4030.2018.01.007

Role of mast cells in Staphylococcus aureus enterotoxin Binduced atopic dermatitis-like skin inflammation in mice

Authors Info & Affiliations

Wang Shan

Department of Dermatology, Peking University First Hospital, Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing 100034, China (Current affiliation of the first author was Department of Dermatology, Beijing Children′s Hospital, Capital Medical University, National Center for Children′s Health, Beijing 100045, China)

Zhao Zuotao

Wang Yuhan

Tu Ping

Liu Lingling

Published： 2018 -01 -15 ·

DOI： 10.3760/cma.j.issn.0412-4030.2018.01.007

332

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摘要

目的探讨肥大细胞在金黄色葡萄球菌肠毒素B（SEB）诱导的BALB/c小鼠特应性皮炎样炎症反应中的作用。

方法24只BALB/c小鼠分为4组，分别使用卵清蛋白（OVA）、SEB、OVA+ SEB联合组及生理氯化钠溶液（对照组）建立经皮诱导的AD样模型。对模型小鼠AD样皮损进行临床观察和皮损严重程度评分，组织病理切片并行甲苯胺蓝及免疫组化染色观察肥大细胞的数目、分布及形态，计算肥大细胞脱颗粒百分比。

结果分别单独使用OVA、SEB及OVA+ SEB联合组经皮诱导模型小鼠AD样局部炎症反应临床表现、皮损严重程度评分及组织病理炎症细胞浸润程度，均较对照组严重，且OVA+ SEB组较OVA及SEB组更为严重（ P<0.05）。AD样皮损真皮的肥大细胞数目分别为10.625（3.675）/高倍视野、11.000（4.163）/高倍视野和13.875（8.813）/高倍视野，均较对照组的5.925（2.088）/高倍视野明显增多（ P<0.05）；SEB组和OVA+ SEB组的肥大细胞脱颗粒百分比达（71.083 ± 14.519）%和（58.767 ± 16.978）%，高于OVA组（24.050 ± 11.161）%和对照组（23.617 ± 8.132）%（ P<0.05）。二元变量相关分析显示，各组皮损肥大细胞总数与临床皮损严重程度评分呈线性相关（ P<0.05）。

结论SEB经皮刺激可诱导小鼠产生AD样皮损，并可加重OVA诱导的小鼠AD样皮损严重程度。肥大细胞增殖、活化脱颗粒释放类胰蛋白酶等参与炎症过程。

关键词：皮炎，特应性;肥大细胞;金黄色葡萄球菌;肠毒素类;类胰蛋白酶类;卵白蛋白

ABSTRACT

ObjectiveTo investigate the role of mast cells in Staphylococcus aureus enterotoxin B (SEB) -induced atopic dermatitis (AD) -like skin inflammation in BALB/c mice.

MethodsA total of 24 BALB/c mice were randomly and equally divided into 4 groups to be topically treated with ovalbumin (OVA group) , SEB (SEB group) , OVA+ SEB (OVA+ SEB group) and sodium chloride physiological solution (control group) respectively, so as to establish mouse models of epicutaneously induced AD-like skin inflammation. The AD-like skin lesions were evaluated by clinical observation and eczema area and severity index (EASI) . Biopsy specimens were obtained from lesional skin of mice and then subjected to toluidine blue staining and immunohistochemical staining to count the mast cells, observe the morphology and distribution of mast cells, and calculate the percentage of degranulated mast cells.

ResultsAfter 7-week treatment, the OVA group, SEB group and OVA+ SEB group all showed severer local skin inflammation, higher EASI scores and denser infiltration of inflammatory cells compared with the control group. Moreover, the OVA+ SEB group showed significantly severer local skin inflammation, skin lesions and degree of infiltration of inflammatory cells compared with the OVA group and SEB group (all P < 0.05) . The number of mast cells in the dermis of AD-like skin lesions per high-power field (× 400) was significantly higher in the OVA group (median[quartile range]: 10.625[3.675]) , SEB group (11.000[4.163]) and OVA+ SEB group (13.875[8.813]) than that in the control group (5.925[2.088], all P < 0.05) . The SEB group (71.083% ± 14.519%) and OVA+ SEB group (58.767% ± 16.978%) both showed significantly higher percentage of degranulated mast cells compared with the OVA group (24.050% ± 11.161%, both P < 0.05) and control group (23.617% ± 8.132%, both P < 0.05) . Bivariate correlation analysis showed that the number of mast cells in the skin lesions was positively linearly correlated with the EASI scores ( P < 0.05) .

ConclusionsEpicutaneous application of SEB can induce AD-like skin lesions in mice, and can exacerbate the severity of OVA-induced AD-like skin lesions. Mast cell proliferation, activation/degranulation and tryptase release may participate in the inflammation.

KEYWORDS： Dermatitis, atopic;Mast cells; Staphylococcus aureus ;Enterotoxins;Tryptases;Ovalbumin

Corresponding author: Liu Lingling, Email: nc.defmoabc.liamdemgnilgniluil

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引用本文

王珊,赵作涛,王誉涵,等. 肥大细胞在金黄色葡萄球菌肠毒素B诱导小鼠特应性皮炎样炎症反应中的作用[J]. 中华皮肤科杂志,2018,51(1)：26-30.

DOI:10.3760/cma.j.issn.0412-4030.2018.01.007

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感染与免疫的相互作用是特应性皮炎（atopic dermatitis，AD）的发病机制研究中的热点之一，而金黄色葡萄球菌（金葡菌）的感染或定植在AD中的作用已得到公认 ^{[
1
]}。与诱发加重AD炎症相关的金葡菌产物目前认为主是与金葡菌超抗原（staphylococcal superantigen，SsAg）的作用有关。已有研究显示，SsAg诱发加重AD的机制主要与T细胞 ^{[
2
]}、B细胞 ^{[
3
]}、树突细胞、角质形成细胞 ^{[
4
]}、嗜酸性粒细胞 ^{[
5
]}等作用有关。然而，SsAg对另一在AD中起重要作用的肥大细胞尚未见报道。我们研究 ^{[
6
]}发现，金葡菌肠毒素B（ Staphylococcus aureus enterotoxins B，SEB）可直接活化肥大细胞，使其释放类胰蛋白酶及组胺，但在体内微生物如金葡菌感染或定植是否作用于肥大细胞并参与AD尚不清楚。因此，本研究用SEB来构建小鼠AD模型，初步探讨肥大细胞在SEB诱导的AD样炎症反应中的作用。

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通信作者：刘玲玲，Email： nc.defmoabc.liamdemgnilgniluil

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