Cellular responses to Staphylococcus aureus alpha-toxin in chronic rhinosinusitis with nasal polyps.
Cellular responses to Staphylococcus aureus alpha-toxin in chronic rhinosinusitis with nasal polyps.
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DOI：
10.2332/allergolint.14-oa-0703
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
M. Okano;T. Fujiwara;S. Kariya;T. Higaki;Takenori Haruna;O. Matsushita;Yohei Noda;S. Makihara
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文献类型：
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作者：
M. Okano;T. Fujiwara;S. Kariya;T. Higaki;Takenori Haruna;O. Matsushita;Yohei Noda;S. Makihara
背景与金黄色葡萄球菌衍生的超抗原外毒素相比，非超抗原外毒素在嗜酸性粒细胞性气道疾病发病机制中的作用仍然不清楚。我们试图表征金黄色葡萄球菌α毒素诱导的慢性鼻窦炎伴鼻息肉（CRSwNP）的细胞反应。方法 分别从伴鼻息肉和不伴鼻息肉的 CRS 患者中制备分散的鼻息肉细胞和钩状组织细胞。将细胞与不同浓度的α毒素或葡萄球菌肠毒素B一起孵育，然后测定细胞上清液中IL-5、IL-13、IFN-γ、IL-17A和IL-10的水平。还确定了 α-毒素诱导的细胞因子产生的病理生理学意义，包括鼻窦炎的放射学严重程度、组织和血液嗜酸性粒细胞增多、血清总 IgE 水平以及 1 秒用力呼气量/用力肺活量比 (FEV1/FVC)。结果 鼻息肉细胞响应 α 毒素产生大量的 IL-5、IL-13、IFN-γ、IL-17A 和 IL-10。鼻息肉细胞中细胞因子的产生高于钩状组织细胞。 α-毒素刺激 IL-5、IL-13 和 IL-10 产生的效力与肠毒素相当。 α-毒素诱导的 IFN-γ、IL-17A 和 IL-10 产生与嗜酸性粒细胞浸润鼻息肉的程度显着负相关。相反，α-毒素诱导的 IFN-γ 和 IL-10 产生与 FEV1/FVC 显着正相关。与非哮喘患者相比，哮喘患者的 IL-10 产量显着降低。 结论 金黄色葡萄球菌衍生的 α 毒素可激发鼻息肉的细胞反应。这些反应，尤其是 IL-10 合成失败，可能在 CRSwNP 的病理生理学中发挥作用。
BACKGROUND In contrast to Staphylococcus aureus-derived superantigenic exotoxins, the role of non-superantigenic exotoxins in the pathogenesis of eosinophilic airway diseases remains obscure. We sought to characterize S. aureus alpha-toxin-induced cellular responses in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS Dispersed nasal polyp cells and uncinate tissue cells were prepared from patients with CRS with and without nasal polyps, respectively. Cells were incubated with various concentrations of alpha-toxin or staphylococcal enterotoxin B and then the levels of IL-5, IL-13, IFN-γ, IL-17A, and IL-10 in the cell supernatants were determined. The pathophysiological significance of alpha-toxin-induced cytokine production was also determined including radiological severity of rhinosinusitis, tissue and blood eosinophilia, serum total IgE level, and 1-s forced expiratory volume/forced vital capacity ratio (FEV1/FVC). RESULTS Nasal polyp cells produced substantial amounts of IL-5, IL-13, IFN-γ, IL-17A, and IL-10 in response to alpha-toxin. Cytokine production was higher in nasal polyp cells than in uncinate tissue cells. The potency of alpha-toxin in stimulating IL-5, IL-13, and IL-10 production was comparable to that of enterotoxin. Alpha-toxin-induced IFN-γ, IL-17A, and IL-10 production significantly and negatively correlated with the degree of eosinophil infiltration into nasal polyps. Conversely, alpha-toxin-induced IFN-γ and IL-10 production significantly and positively correlated with FEV1/FVC. IL-10 production was significantly lower in asthmatic patients compared to non-asthmatics CONCLUSIONS S. aureus-derived alpha-toxin can provoke cellular responses in nasal polyps. These responses, especially failure to synthesize IL-10, may play a role in the pathophysiology of CRSwNP.