Mucus clearance as a primary innate defense mechanism for mammalian airways.
Mucus clearance as a primary innate defense mechanism for mammalian airways.
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DOI：
10.1172/jci15217
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发表时间：
2002-03
期刊：
影响因子：
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通讯作者：
M. Knowles;R. Boucher
中科院分区：
文献类型：
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作者：
M. Knowles;R. Boucher
当吸入的空气从相对狭窄的鼻/气管通道进入较大的肺泡表面积(70m2)时，传导气管在气管和肺泡之间分支20-25次，在那里发生气体交换。这种分支解剖导致了从近端呼吸道(例如，第三代；∼50平方厘米)到远端呼吸道(第20代到第25代；∼2平方厘米)的表面积极大地扩展。呼吸道表面积(或呼吸道周长)的区域差异；1)，这通常被描绘成一个倒置的漏斗(图(图1)，1)，这对肺防御构成了有趣的挑战。由于许多附着在呼吸道表面的颗粒具有传染性，呼吸道进化出了天然的防御机制，不断保护呼吸道免受细菌和其他类型的感染。图1预防慢性细菌感染的肺防御机制。肺被描绘成一个倒置的漏斗，反映了远端和近端呼吸道的相对表面积。粘液机械清除假说如左图所示。..。对于这些先天的呼吸道防御机制的性质(2，3)仍然没有达成一致意见(图(图1).1)。在更传统的观点中，粘液的机械清除被认为是主要的先天呼吸道防御机制(4-6)。这种观点认为，呼吸道表面上皮细胞的作用是提供粘液运输所需的综合活动，包括纤毛活动和通过跨上皮离子运输调节呼吸道表面适量的盐和水。最近，由于囊性纤维化(CF)发病机制的研究，出现了第二种关于先天呼吸道防御的观点(7)。这一观点强调了“化学屏障”在保护肺部免受吸入细菌侵害方面的作用(8)。在这一假设中，上皮细胞的两个重要功能是分泌到气道腔中的盐敏感防御素的产生，以及在呼吸道表面产生使防御素活性的低盐(<；50 mM氯化钠)液体(9)。对每个模型的预测和相关数据进行了广泛的审查(2、3、10、11)。在这里，我们将集中讨论肺内粘液清除作为健康和疾病(包括CF)中更重要的先天防御机制的作用。我们将试图填补我们在粘液清除系统的重要方面的知识空白，并在相关的情况下，指出两种观点之间的差异。
The conducting airways branch 20–25 times between the trachea and the alveoli as inhaled air passes from the relatively constricted nasal/tracheal passages to the large surface area of alveoli (70 m2), where gas exchange occurs. This branching anatomy leads to a surface area that expands greatly from proximal airways (e.g., third generation; ∼50 cm2) to distal airways (20th to 25th generation; ∼2 m2). The regional differences in airway surface area (or airway perimeters; ref. 1), which is often depicted by showing the airways as an inverted funnel (Figure (Figure1),1), pose interesting challenges for lung defense. Because many of the particles that settle on airway surfaces are infectious, airways have evolved innate defense mechanisms that constantly protect airways against bacterial and other types of infection. Figure 1 Pulmonary defense mechanisms preventing chronic bacterial infection. The lung is depicted as an inverted funnel, reflecting the relative surface area of distal versus proximal airways. The mechanical-clearance-of-mucus hypothesis is shown on the left. ... There is still little agreement on the nature of these innate airway defense mechanisms (2, 3) (Figure (Figure1).1). In the more traditional view, mechanical clearance of mucus is considered the primary innate airway defense mechanism (4–6). In this view, the role of the epithelia lining airway surfaces is to provide the integrated activities required for mucus transport, including ciliary activity and regulation of the proper quantity of salt and water on airway surfaces via transepithelial ion transport. More recently, a second view of innate airway defense has emerged as a result of studies of the pathogenesis of cystic fibrosis (CF) (7). This view emphasizes a role for a “chemical shield” in protecting the lung against inhaled bacteria (8). In this hypothesis, the two important functions for epithelia are the production of salt-sensitive defensins that are secreted into airway lumens, and the production of a low-salt (<50 mM NaCl) liquid on airway surfaces that renders defensins active (9). The predictions of each of these models and the relevant data have been extensively reviewed (2, 3, 10, 11). Here, we will focus on the role of mucus clearance in the lung as the more important innate defense mechanism in health and disease, including CF. We will attempt to fill in the gaps in our knowledge regarding important aspects of the mucus clearance system, and, where relevant, point out differences between the two views of innate airway defense.