Inoue Ken-ichiro, Takano Hirohisa, Koike Eiko, Yanagisawa Rie, Oda Toshio, Tamura Hiroshi, Adachi Yoshiyuki, Ishibashi Ken-ichi, Ohno Naohito
Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Ibaraki 305-8506, Japan.
Respir Res. 2009 Jul 21;10(1):68. doi: 10.1186/1465-9921-10-68.
Although fungi have been implicated as initiating/deteriorating factors for allergic asthma, their contributing components have not been fully elucidated. We previously isolated soluble beta-glucan from Candida albicans (CSBG) (Ohno et al., 2007). In the present study, the effects of CSBG exposure on airway immunopathology in the presence or absence of other immunogenic allergen was investigated in vivo, and their cellular mechanisms were analyzed both in vivo and in vitro.
In vivo, ICR mice were divided into 4 experimental groups: vehicle, CSBG (25 microg/animal), ovalbumin (OVA: 2 microg/animal), and CSBG + OVA were repeatedly administered intratracheally. The bronchoalveolar lavage cellular profile, lung histology, levels of cytokines and chemokines in the lung homogenates, the expression pattern of antigen-presenting cell (APC)-related molecules in the lung digests, and serum immunoglobulin values were studied. In vitro, the impacts of CSBG (0-12.5 microg/ml) on the phenotype and function of immune cells such as splenocytes and bone marrow-derived dendritic cells (BMDCs) were evaluated in terms of cell proliferation, the surface expression of APC-related molecules, and OVA-mediated T-cell proliferating activity.
In vivo, repeated pulmonary exposure to CSBG induced neutrophilic airway inflammation in the absence of OVA, and markedly exacerbated OVA-related eosinophilic airway inflammation with mucus metaplasia in mice, which was concomitant with the amplified lung expression of Th2 cytokines and IL-17A and chemokines related to allergic response. Exposure to CSBG plus OVA increased the number of cells bearing MHC class II with or without CD80 in the lung compared to that of others. In vitro, CSBG significantly augmented splenocyte proliferation in the presence or absence of OVA. Further, CSBG increased the expression of APC-related molecules such as CD80, CD86, and DEC205 on BMDCs and amplified OVA-mediated T-cell proliferation through BMDCs.
CSBG potentiates allergic airway inflammation with maladaptive Th immunity, and this potentiation was associated with the enhanced activation of APCs including DC.
尽管真菌被认为是过敏性哮喘的起始/恶化因素，但其促成成分尚未完全阐明。我们之前从白色念珠菌中分离出可溶性β-葡聚糖（CSBG）（Ohno等人，2007年）。在本研究中，我们在体内研究了CSBG暴露在存在或不存在其他免疫原性过敏原的情况下对气道免疫病理学的影响，并在体内和体外分析了其细胞机制。
在体内，将ICR小鼠分为4个实验组：载体组、CSBG组（25微克/只动物）、卵清蛋白（OVA：2微克/只动物）组和CSBG + OVA组，通过气管内反复给药。研究支气管肺泡灌洗细胞谱、肺组织学、肺匀浆中细胞因子和趋化因子水平、肺消化物中抗原呈递细胞（APC）相关分子的表达模式以及血清免疫球蛋白值。在体外，根据细胞增殖、APC相关分子的表面表达以及OVA介导的T细胞增殖活性，评估CSBG（0 - 12.5微克/毫升）对免疫细胞如脾细胞和骨髓来源的树突状细胞（BMDC）的表型和功能的影响。
在体内，在不存在OVA的情况下，反复肺部暴露于CSBG会诱发嗜中性气道炎症，并且在小鼠中显著加剧与OVA相关的嗜酸性气道炎症并伴有黏液化生，这与Th2细胞因子、IL - 17A以及与过敏反应相关的趋化因子在肺中的表达增加有关。与其他组相比，暴露于CSBG加OVA会增加肺中带有或不带有CD80的MHC II类分子的细胞数量。在体外，无论是否存在OVA，CSBG都能显著增强脾细胞增殖。此外，CSBG增加了BMDC上CD80、CD86和DEC205等APC相关分子的表达，并通过BMDC增强了OVA介导的T细胞增殖。
CSBG通过适应性不良的Th免疫增强过敏性气道炎症，这种增强与包括DC在内的APC的活化增强有关。
