Innate host Defense of the lung: Effects of lung-lining fluid pH
Innate host Defense of the lung: Effects of lung-lining fluid pH
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DOI：
10.1007/s00408-004-2511-6
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发表时间：
2004-09-01
期刊：
影响因子：
5
通讯作者：
Herring, TA
中科院分区：
文献类型：
--
作者：
Ng, AW;Bidani, A;Herring, TA
肺衬液（LLF）是肺宿主防御系统的主要组成部分。它在整个呼吸道中连续分布，但在传导气道和肺泡之间的化学和生理学方面是异质的。传导性气道内衬有气道表面液体（ASL），其是一种粘液凝胶-水溶液复合物，其在功能上与上皮纤毛相互作用，作为粘膜纤毛自动扶梯。肺泡内衬有肺泡亚相液（AVSF）和肺表面活性物质。AVSF的无菌性部分是由肺泡巨噬细胞的吞噬活性维持的。正常ASL和AVSF都比血浆酸性更强。然而，酸碱调节的细节在两种介质之间不同。可观察到跨上皮的酸碱通量可能通过气道上皮，而肺泡上皮对跨上皮的酸碱通量相对不渗透。此外，必须考虑驻留巨噬细胞对AVSF pH值的影响。驻留巨噬细胞占据AVSF的很大一部分体积，并且是代谢H+的重要来源。ASL和AVSF的缓冲能力可能主要是由于分泌的肽（例如，ASL粘蛋白和AVSF表面活性剂蛋白）。驻留巨噬细胞的细胞外水相和细胞内缓冲系统之间的酸碱交换代表了AVSF的额外缓冲池。ASL和AVSF的pH值可因疾病或炎症而降低。预测低pH抑制微生物从气道和肺泡的清除，增加两个区域中的病原体存活，并改变驻留巨噬细胞和募集的白细胞的介质释放，从而增加旁观者细胞损伤的倾向。总体而言，ASL/AVSF pH预期是肺宿主防御反应的主要决定因素。
Lung-lining fluid (LLF) is a primary constituent of the pulmonary host defense system. It is distributed continuously throughout the respiratory tract but is heterogeneous regarding its chemistry and physiology between the conducting airways and alveoli. The conducting airways are lined with airway surface liquid (ASL), a mucus gel-aqueous sot complex that interacts functionally with epithelia] cilia as the mucociliary escalator. The alveoli are lined with alveolar subphase fluid (AVSF) and pulmonary surfactant. AVSF sterility is maintained in part by the phagocytic activity of resident alveolar macrophages. Normal ASL and AVSF are both more acidic than blood plasma. However, the details of acid-base regulation differ between the two media. Appreciable transepithelial acid-base flux is possible across the airway epithelium, whereas the alveolar epithelium is relatively impermeable to transepithelial acid-base flux. Moreover, one must consider the influence of resident macrophages on AVSF pH. Resident macrophages Occupy a sizable fraction of AVSF by volume and are a substantial source of metabolic H+. The buffering capacities of ASL and AVSF probably are largely due to secreted peptides (e.g., ASL mucins and AVSF surfactant proteins). Acid-base exchange between the extracellular hydrophase and intracellular buffering systems of resident macrophages represents an additional buffer pool for AVSF. The pH of ASL and AVSF can be depressed by disease or inflammation. Low pH is predicted to suppress microbe clearance from the airways and alveoli, increase pathogen survival in both regions, and alter mediator release by resident macrophages and recruited leukocytes thereby increasing the propensity for bystander cell injury. Overall, ASL/AVSF pH is expected to be a major determinant of lung host defense responses.