CD14 is an essential mediator of LPS-induced airway disease
CD14 is an essential mediator of LPS-induced airway disease
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DOI：
10.1152/ajplung.00282.2006
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发表时间：
2007-07-01
影响因子：
4.9
通讯作者：
Schwartz, David A.
中科院分区：
文献类型：
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作者：
Brass, David M.;Hollingsworth, John W.;Schwartz, David A.
啮齿动物慢性吸入脂多糖(LPS)重现了人类慢性阻塞性肺疾病的许多经典特征，包括呼吸道高反应性、中性粒细胞炎症、肺内细胞因子的产生和小气道重塑。CD14缺陷小鼠(C57BL/6(CD14-/-))对全身性内毒素有不同的反应，但CD14在吸入性内毒素反应中的作用尚不明确。我们观察到，C57BL/6(CD14-/-)小鼠对单一的内毒素吸入攻击没有表现出明显的生理或炎症反应。而C57BL/6(CD14-/-)小鼠对吸入内毒素的生理反应(呼吸道高反应性)和炎症反应(中性粒细胞和肿瘤坏死因子-α全肺灌洗液的存在)可通过气管内注入可溶性CD14来恢复。C57BL/6(CD14-/-)小鼠气管内注射野生型巨噬细胞仅能恢复中性粒细胞炎症，但不能恢复气道高反应性或全肺灌洗中的肿瘤坏死因子-α蛋白。这些发现表明，CD14在脂多糖诱导的呼吸道疾病中起关键作用，巨噬细胞CD14足以启动中性粒细胞重新聚集到呼吸道，但CD14可能还需要与其他类型的细胞相互作用，以发展呼吸道高反应性和细胞因子的产生。
Chronic lipopolysaccharide ( LPS) inhalation in rodents recapitulates many classic features of chronic obstructive pulmonary disease seen in humans, including airways hyperresponsiveness, neutrophilic inflammation, cytokine production in the lung, and small airways remodeling. CD14- deficient mice ( C57BL/6(CD14-/-)) have an altered response to systemic LPS, and yet the role of CD14 in the response to inhaled LPS has not been defined. We observed that C57BL/6(CD14-/-) mice demonstrate no discernable physiological or inflammatory response to a single LPS inhalation challenge. However, the physiological ( airways hyperresponsiveness) and inflammatory ( presence of neutrophils and TNF-alpha whole lung lavage fluid) responsiveness to inhaled LPS in C57BL/ 6(CD14-/-) mice was restored by instilling soluble CD14 intratracheally. Intratracheal instillation of wild- type macrophages into C57BL/6(CD14-/-) mice restored neutrophilic inflammation only and failed to restore airways hyperresponsiveness or TNF-alpha protein in whole lung lavage. These findings demonstrate that CD14 is critical to LPS- induced airway disease and that macrophage CD14 is sufficient to initiate neutrophil recruitment into the airways but that CD14 may need to interact with other cell types as well for the development of airways hyperresponsiveness and for cytokine production.