Innate immunity of surfactant protein A in experimental otitis media
Innate immunity of surfactant protein A in experimental otitis media
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DOI：
10.1177/1753425919866006
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发表时间：
2019-08-03
期刊：
影响因子：
3.2
通讯作者：
Wang, Guirong
中科院分区：
文献类型：
--
作者：
Abdel-Razek, Osama;Ni, Lan;Wang, Guirong
表面活性蛋白A（SurfactantProteinA，SP-A）通过调理作用和补体激活，在机体天然免疫应答和机体防御各种微生物中发挥重要作用。为了研究SP-A在不可分型流感嗜血杆菌（NTHi）诱导的急性中耳炎中的作用，本研究使用野生型C57 BL/6（WT）和SP-A敲除（KO）小鼠。我们将小鼠分为感染组和对照组，在感染组中中耳（ME）注射NTHi，对照组接受相同的治疗，使用生理盐水。在处理后第1、3和7天处死小鼠。固定颞骨样本进行组织学、细胞和分子分析。收集耳冲洗液（EWF）用于培养和分析促炎细胞因子和炎性细胞。在体外研究了SP-A介导的细菌聚集、杀伤和巨噬细胞的吞噬作用。在WT小鼠的ME和咽鼓管粘膜中检测到SP-A表达，但在KO小鼠中未检测到。感染后，KO小鼠表现出更严重的炎症，表现为ME粘膜厚度增加和炎性细胞浸润以及与WT小鼠相比更高的NF-κ B活化。感染KO小鼠的EWF中IL-6和IL-1 β的水平在第1天高于感染WT小鼠。我们的研究表明，SP-A介导NTHi聚集和杀伤，并增强巨噬细胞的细菌吞噬作用，在体内调节中耳炎中ME的炎症。
Surfactant protein A (SP-A) plays an important role in innate immune response and host defense against various microorganisms through opsonization and complement activation. To investigate the role of SP-A in non-typeable Haemophilus influenzae (NTHi)-induced acute otitis media, this study used wild type C57BL/6 (WT) and SP-A knockout (KO) mice. We divided mice into an infection group in which the middle ear (ME) was injected with NTHi and a control group that received the same treatment using normal saline. Mice were sacrificed on d 1, 3, and 7 after treatment. Temporal bone samples were fixed for histological, cellular, and molecular analyses. Ear washing fluid (EWF) was collected for culture and analyses of pro-inflammatory cytokines and inflammatory cells. SP-A-mediated bacterial aggregation and killing and phagocytosis by macrophages were studied in vitro. SP-A expression was detected in the ME and Eustachian tube mucosa of WT mice but not KO mice. After infection, KO mice showed more severe inflammation evidenced by increased ME mucosal thickness and inflammatory cell infiltration and higher NF-kappa B activation compared to WT mice. The levels of IL-6 and IL-1 beta in the EWF of infected KO mice were higher compared to infected WT mice on d 1. Our studies demonstrated that SP-A mediated NTHi aggregation and killing and enhanced bacterial phagocytosis by macrophages in vitro and modulated inflammation of the ME in otitis media in vivo.