Surfactant protein-A limits Ureaplasma-mediated lung inflammation in a murine pneumonia model.
Surfactant protein-A limits Ureaplasma-mediated lung inflammation in a murine pneumonia model.
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DOI：
10.1203/pdr.0b013e3181aabd66
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发表时间：
2009-08
影响因子：
3.6
通讯作者：
Viscardi RM
中科院分区：
文献类型：
--
作者：
Famuyide ME;Hasday JD;Carter HC;Chesko KL;He JR;Viscardi RM
支原体呼吸道定植刺激早产儿肺部长期失调的炎症，导致支气管肺发育不良（BPD）的发病机制。表面活性蛋白-A（SP-A），一种对细菌清除和调节炎症至关重要的肺聚集蛋白，在早产儿肺中缺乏。为了分析SP-A在调节脲原体介导的肺部炎症中的作用，将SP-A缺陷（SP-A-/-）和WT小鼠用小鼠适应的U.在接种后28天连续评估细小病毒分离物和炎症指数。与感染的WT和未感染的对照组相比，支原体感染的SP-A−/−小鼠表现出过度的炎症反应，表现为中性粒细胞和巨噬细胞迅速流入肺，支气管肺泡灌洗液TNF-α、人生长相关蛋白α（KC）的小鼠类似物和单核细胞趋化因子（MCP-1）浓度较高。然而，与WT小鼠相比，SP-A−/−小鼠对脲原体感染的亚硝酸盐生成在24小时时减弱，脲原体清除延迟。将人SP-A与脲原体接种物共同给予SP-A−/−小鼠可降低炎症反应，但不能提高细菌清除率。SP-A缺乏可能导致支原体感染早产儿肺的炎症反应延长，但其他因素可能导致支原体清除受损。
Ureaplasma respiratory tract colonization stimulates prolonged, dysregulated inflammation in the lungs of preterm infants, contributing to bronchopulmonary dysplasia (BPD) pathogenesis. Surfactant protein-A (SP-A), a lung collectin critical for bacterial clearance and regulating inflammation, is deficient in the preterm lung. To analyze the role of SP-A in modulating Ureaplasma-mediated lung inflammation, SP-A deficient (SP-A−/−) and WT mice were inoculated intratracheally with a mouse-adapted U. parvum isolate and indices of inflammation were sequentially assessed up to 28d post-inoculation. Compared to infected WT and non-infected controls, Ureaplasma-infected SP-A−/− mice exhibited an exaggerated inflammatory response evidenced by rapid influx of neutrophils and macrophages into the lung, and higher bronchoalveolar lavage TNF-α, mouse analogue of human growth-related protein alpha (KC), and monocyte chemotactic factor (MCP-1) concentrations. However, nitrite generation in response to Ureaplasma infection was blunted at 24h and Ureaplasma clearance was delayed in SP-A−/− mice compared to WT mice. Co-administration of human SP-A with the Ureaplasma inoculum to SP-A−/− mice reduced the inflammatory response, but did not improve the bacterial clearance rate. SP-A deficiency may contribute to the prolonged inflammatory response in the Ureaplasma-infected preterm lung, but other factors may contribute to the impaired Ureaplasma clearance.