SP-A Preserves Airway Homeostasis During Mycoplasma pneumoniae Infection in Mice
SP-A Preserves Airway Homeostasis During Mycoplasma pneumoniae Infection in Mice
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DOI：
10.4049/jimmunol.0900452
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发表时间：
2009-06-15
影响因子：
4.4
通讯作者：
Wright, Jo Rae
中科院分区：
文献类型：
--
作者：
Ledford, Julie G.;Goto, Hisatsugu;Wright, Jo Rae
在正常呼吸过程中，肺部不断受到无数环境刺激物和感染性损伤的挑战。肺宿主防御机制在抑制/清除病原体和调节可能损伤气道上皮的炎症反应之间维持稳态。这种防御机制的一个组成部分，表面活性剂蛋白- a (SP-A)，在介导宿主对炎症和感染因子的反应中发挥多功能作用。SP-A通过结合表面不饱和磷脂酰甘油对肺炎支原体（Mp）具有抑菌作用。SP-A还能结合Mp膜蛋白MPN372。在这项研究中，我们用SP-A缺乏的小鼠研究SP-A在Mp急性期肺部感染中的作用。Mp感染SP-A（-/-）小鼠的生物反应、炎症和细胞浸润比野生型小鼠大得多。同样，SP-A（-/-）小鼠对Mp感染的生理反应（气道高反应性和肺顺应性）受到更严重的影响。tnf - α的药理抑制可减轻mp诱导的生物和生理变化。我们的研究结果表明，SP-A通过抑制炎症细胞募集和限制过度的tnf - α反应，对保持肺稳态和宿主防御这种临床相关的Mp菌株至关重要。中华免疫学杂志，2009,32(2):718 - 727。
The lung is constantly challenged during normal breathing by a myriad of environmental irritants and infectious insults. Pulmonary host defense mechanisms maintain homeostasis between inhibition/clearance of pathogens and regulation of inflammatory responses that could injure the airway epithelium. One component of this defense mechanism, surfactant protein-A (SP-A), exerts multifunctional roles in mediating host responses to inflammatory and infectious agents. SP-A has a bacteriostatic effect on Mycoplasma pneumoniae (Mp), which occurs by binding surface disaturated phosphatidylglycerols. SP-A can also bind the Mp membrane protein, MPN372. In this study, we investigated the role of SP-A during acute phase pulmonary infection with Mp using mice deficient in SP-A. Biologic responses, inflammation, and cellular infiltration, were much greater in Mp infected SP-A(-/-) mice than wild-type mice. Likewise, physiologic responses (airway hyperresponsiveness and lung compliance) to Mp infection were more severely affected in SP-A(-/-) mice. Both Mp-induced biologic and physiologic changes were attenuated by pharmacologic inhibition of TNF-alpha. Our findings demonstrate that SP-A is vital to preserving lung homeostasis and host defense to this clinically relevant strain of Mp by curtailing inflammatory cell recruitment and limiting an overzealous TNF-alpha response. The Journal of Immunology, 2009, 182: 7818-7827.