Cellular and Non-cellular Barriers to Particle Transport Across the Lungs
Compared to the human body’s other outer epithelia, like e.g. the skin and the GI tract, the lungs have the largest surface area. Moreover, the so called “air-blood-barrier” is extremely thin, but also very tight to fulfill its physiological function. Thi
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Cellular and Non-cellular Barriers to Particle Transport Across the Lungs Nicole Schneider-Daum, Marius Hittinger, Xabier Murgia and Claus-Michael Lehr
Abstract Compared to the human body’s other outer epithelia, like e.g. the skin and the GI tract, the lungs have the largest surface area. Moreover, the so called “air-blood-barrier” is extremely thin, but also very tight to fulfill its physiological function. This chapter discusses the lung as a biological barrier in the context of inhaled particles. This important function is provided by some specific cellular as well as non-cellular elements. How the lung copes with particles “after landing” is not only relevant regarding the risks of accidentally inhaled nanomaterials, but also for designing safe and efficient nanopharmaceuticals to be inhaled on purpose.
7.1 Introduction: What Distinguishes the Lung from Other Epithelia? Along the Respiratory Tract the Epithelium Changes The pulmonary epithelium holds multiple functions not only essential for tissue homeostasis. Various other requirements such as host defense or controlled transport are fulfilled by differences in the type and abundance of specialized cells at each location [1]. In general, similar types of pulmonary epithelial cells are found in all vertebrate lungs. In human lung, the airways are lined by a so-called pseudo-stratified N. Schneider-Daum (B) · M. Hittinger · X. Murgia · C.-M. Lehr Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Campus E8 1, 66123 Saarbrücken, Germany e-mail: [email protected] M. Hittinger e-mail: [email protected] X. Murgia e-mail: [email protected] C.-M. Lehr e-mail: [email protected] M. Hittinger · C.-M. Lehr PharmBioTec GmbH, Science Park 1, 66123 Saarbrücken, Germany © Springer Nature Switzerland AG 2019 P. Gehr and R. Zellner (eds.), Biological Responses to Nanoscale Particles, NanoScience and Technology, https://doi.org/10.1007/978-3-030-12461-8_7
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Fig. 7.1 Scheme of the 3 main parts of the respiratory tract, taken from [5]
columnar epithelium. It consists of a single layer of cells that give the appearance of multiple layers, due to the fact that the nuclei of these epithelial cells are at different levels leading to the illusion of being stratified. Predominant cell types are ciliated, basal, goblet and other secretory cells, including club cells (also known as Clara cells). While goblet cells secrete gel-forming mucins and are found in several epithelia, e.g. in the GI tract, the club cells produce glycosaminoglycans to protect the bronchiole lining. The alveolar region contains squamous alveolar type I (ATI) and cuboidal alveolar type II (ATII) cells (Fig. 7.1). The latter synthesize and secrete pulmonary surfactant, which lowers the surface tension in the alveoli relevant during inflation and play an important role as progenitors for ATI cells. These are found in close proximity to alveolar capillaries to allow for gas exchange. Their ability to form a
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