Absence of SP-A modulates innate and adaptive defense responses to pulmonary influenza infection
Absence of SP-A modulates innate and adaptive defense responses to pulmonary influenza infection
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DOI：
10.1152/ajplung.00280.2001
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发表时间：
2002-03-01
影响因子：
4.9
通讯作者：
Korfhagen, T
中科院分区：
文献类型：
--
作者：
LeVine, AM;Hartshorn, K;Korfhagen, T
通过鼻内滴注用甲型流感病毒（IAV）感染缺乏表面活性蛋白SP-A [SP-A（-/-）]的小鼠和野生型SP-A（+/+）小鼠。在SP-A（-/-）小鼠中观察到IAV清除率降低，并与肺部炎症增加相关。用外源性SP-A处理SP-A（-/-）小鼠增强病毒清除并减少肺部炎症。肺泡巨噬细胞对IAV的摄取在SP-A（-/-）和SP-A（+/+）小鼠中相似。在SP-A（-/-）小鼠的支气管肺泡灌洗中性粒细胞中，髓过氧化物酶活性降低。IAV感染后7天，SP-A（-/-）小鼠肺和脾中的B淋巴细胞和活化T淋巴细胞增加，而肺中的辅助性T细胞（Th）1应答[干扰素-γ、白细胞介素（IL）-2和IgG（2a）]增加，Th 2应答（IL-4、IL-10和IgG（1））减少。在缺乏SP-A的情况下，受损的病毒清除与肺部炎症增加、中性粒细胞髓过氧化物酶活性降低和Th 1应答增加相关。由于呼吸道是IAV和其他呼吸道病原体的常见入口，因此SP-A可能在针对IAV的先天性防御和适应性免疫应答中发挥作用。
Mice lacking surfactant protein SP-A [SP-A(-/-)] and wild type SP-A(+/+) mice were infected with influenza A virus (IAV) by intranasal instillation. Decreased clearance of IAV was observed in SP-A(-/-) mice and was associated with increased pulmonary inflammation. Treatment of SP-A(-/-) mice with exogenous SP-A enhanced viral clearance and decreased lung inflammation. Uptake of IAV by alveolar macrophages was similar in SP-A(-/-) and SP-A(+/+) mice. Myeloperoxidase activity was reduced in isolated bronchoalveolar lavage neutrophils from SP-A(-/-) mice. B lymphocytes and activated T lymphocytes were increased in the lung and spleen, whereas T helper (Th) 1 responses were increased [interferon-gamma, interleukin (IL)-2, and IgG(2a)] and Th2 responses were decreased (IL-4, and IL-10, and IgG(1)) in the lungs of SP-A(-/-) mice 7 days after IAV infection. In the absence of SP-A, impaired viral clearance was associated with increased lung inflammation, decreased neutrophil myeloperoxidase activity, and increased Th1 responses. Because the airway is the usual portal of entry for IAV and other respiratory pathogens, SP-A is likely to play a role in innate defense and adaptive immune responses to IAV.