Role of Surfactant Protein D in Experimental Otitis Media
Role of Surfactant Protein D in Experimental Otitis Media
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DOI：
10.1159/000513605
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发表时间：
2021-02-08
影响因子：
5.3
通讯作者：
Wang, Guirong
中科院分区：
文献类型：
--
作者：
Abdel-Razek, Osama;Liu, Tianyi;Wang, Guirong
表面活性蛋白D （SP-D）是一种c型蛋白集合，在先天免疫和肺内稳态中起重要作用。本研究研究了SP-D在不可分型流感嗜血杆菌（NTHi）诱导的中耳炎（OM）小鼠模型中的作用。本研究采用野生型C57BL/6 （WT）和SP-D敲除（KO）小鼠。小鼠中耳注射5 μ L NTHi菌液（3.5 × 10(5) CFU/耳）或等量无菌生理盐水（对照组）。小鼠于治疗后第1、3、7天3个时间点处死。我们发现SP-D在WT小鼠的耳咽管（ET）和ME粘膜中表达，而在SP-D KO小鼠中没有表达。感染后，SP-D KO小鼠的粘膜厚度增加，ME和ET的炎症细胞浸润比WT小鼠更强烈（p < 0.05）。与感染的WT小鼠相比，感染SP-D KO小鼠耳洗液中细菌集落形成单位和细胞因子（IL-6和IL-1 β）水平升高。分子分析显示，与WT小鼠相比，感染SP-D KO的NF-kappa B和NLRP3活化水平较高（p < 0.05）。体外研究表明，SP-D显著诱导NTHi细菌聚集，增强巨噬细胞的细菌吞噬作用（p < 0.05）。此外，LPS处理后，人ME上皮细胞NLRP3和SP-D蛋白的表达呈剂量依赖性增加。我们得出结论，SP-D通过增强宿主防御和调节炎症nf - κ B和NLRP3的激活，在实验性OM小鼠的先天免疫和疾病解决中发挥关键作用。
Surfactant protein D (SP-D) is a C-type collectin and plays an important role in innate immunity and homeostasis in the lung. This study studied SP-D role in the nontypeable Haemophilus influenzae (NTHi)-induced otitis media (OM) mouse model. Wild-type C57BL/6 (WT) and SP-D knockout (KO) mice were used in this study. Mice were injected in the middle ear (ME) with 5 mu L of NTHi bacterial solution (3.5 x 10(5) CFU/ear) or with the same volume of sterile saline (control). Mice were sacrificed at 3 time points, days 1, 3, and 7, after treatment. We found SP-D expression in the Eustachian tube (ET) and ME mucosa of WT mice but not in SP-D KO mice. After infection, SP-D KO mice showed more intense inflammatory changes evidenced by the increased mucosal thickness and inflammatory cell infiltration in the ME and ET compared to WT mice (p < 0.05). Increased bacterial colony-forming units and cytokine (IL-6 and IL-1 beta) levels in the ear washing fluid of infected SP-D KO mice were compared to infected WT mice. Molecular analysis revealed higher levels of NF-kappa B and NLRP3 activation in infected SP-D KO compared to WT mice (p < 0.05). In vitro studies demonstrated that SP-D significantly induced NTHi bacterial aggregation and enhanced bacterial phagocytosis by macrophages (p < 0.05). Furthermore, human ME epithelial cells showed a dose-dependent increased expression of NLRP3 and SP-D proteins after LPS treatment. We conclude that SP-D plays a critical role in innate immunity and disease resolution through enhancing host defense and regulating inflammatory NF-kappa B and NLRP3 activation in experimental OM mice.