Human alveolar epithelium

The human alveolar epithelium consists of two cell types type I (alveolar epithelial type I [ATI], pneumocyte I) and type n (alveolar epithelial type II... 

The intention to study transport processes at pulmonary epithelia, however, raised two particular problems (i) the apical side of these epithelia is typically in contact with air rather than with a liquid and (ii) in order to maximize the surface area, the lungs have a complex treelike structure, ending in millions of tiny alveolar bubbles. The total surface area of the human alveolar epithelium is almost half of that of the intestines (100-120 m2), with its macroscopic appearance resembling a sponge, and it is virtually impossible to use such a tissue for transport experiments in a diffusion-chamber setup. 

The rate of protein clearance has been estimated as 10% of the rate of fluid clearance from alveoli [173]. IgG clearance is probably mediated by FcRn transcytosis in distal type I alveolar epithelium and more proximal bronchial epithelium. Type I alveolar epithelium and bronchial epithelium contain the necessary subcellular structures for FcRn-mediated transcytosis vesicles, membrane invaginations, caveolae, and clathrin-coated pits [173,174], FcRn mRNA is expressed in lung although the cell types and locations have not yet been determined [112], Moreover, primary alveolar epithelial monolayer cell cultures express functional FcRn [173], plgA-R/SC transcytosis is thought to contribute little to distal (alveolar) airway IgG transport but might mediate more proximal (bronchial or bronchiolar) IgA transport [173], Uptake of an aerosolized IgG Fc-erythropoietin fusion molecule and subsequent erythropoietin-induced reticulocytosis has been demonstrated in human and nonhuman primates [175],... 

Potential sources of NO in the lungs include activated alveolar macrophages, neutrophils alveolar type II cells endothelial cells and airway cells. nNOS is localized to nonadrenergic/noncholinergic nerve terminals and is present in human airway epithelial cells. eNOS is localized to human pulmonary epithelium and bronchial epithelium. Studies have suggested that iNOS is constitutively expressed in human upper airway epithelium... 

When animals or humans are exposed to aerosohzed fibers or particles, some proportion of the inhaled materials will be deposited in the nasal passages and upper airways. Other particles reach the conducting airways, including the terminal bronchioles, and part of the disease process is manifested there. Finally, a proportion of the asbestos fibers or silica crystals is deposited on the alveolar epithelium. With every breath that contains particles, more are deposited along the respiratory tract, thus triggering a series of pathobiological responses. AU the diseases caused by asbestos and silica are dose responsive, i.e., the more particles inhaled, the more likely it is that the disease will develop and the more advanced the disease will finally appear (2). 

Ghaedi, M., CaUe, E.A., Mendez, J.J., et al. Human iPS cella derived alveolar epithelium repopulates lung extracellular matrix. J. Chn. Invest. 123, 4950-4962 (2013). doi 10.1172/JCI68793... 

We used in vitro models of lung epithelial cell lines or primary cells to determine E25 permeability. Two different cell types were used to mimic the airway and alveolar epithelium of the lung to study transport. Calu-3, a human cell line derived from an airway carcinoma, when grown at an air/liquid interface, differentiate to form a secretory airway epithelium (17). Rat primary epithelial cells isolated as described by Cheek et al. (18) form a tight barrier similar in structure and function to the alveolar surface. Both cell types when grown to confluence form tight junctions and differentiate and polarize so that the apical or air surface has different characteristics than the basolateral or blood side. The typical transepithelial resistance observed was 350 or >1000 ohms-cm for Calu-3 cells or primary rat alveolar cells, respectively. Once an acceptable resistance was achieved, E25 (2 mg/mL) was placed in either the apical or the basolateral chamber. Cell monolayers were incubated at 37°C for up to 3 hours and ELISA measured the amount of E25 that translocated the epithelial layer and appeared in the receiver well. The apparent permeability (Papp) of the epithelium for E25 was calculated as ... 

The alveolar epithelium eonsists of two major cell types. It covers a total surface area of approximately 140 in humans (7). Ninety-three pereent of the surface area (human, baboon, and rat 68), or even more (dog, rabbit, hamster, mouse, and other species 69) is covered by the squamous type I eells, and 7% or less by the cuboidal type II eells. The structural basis for the gas exehange is the interalveolar septum, whieh forms the wall between two alveoli. In this location air and blood come into close eontact, and they are separated by a tissue barrier with an average thickness of only 2 pm (human 7). Over large areas in humans and in many other speeies (69) the thickness is even less than 1 pm. 

Klein JM, Fritz BL, McCarthy TA, Wohlfordlenane CL, Snyder JM. Localization of epidermal growth factor receptor in alveolar epithelium during human fetal lung development in vitro. Exp Lung Res 1995 21 917-939. 

While a number of immortalised cell lines emanating from different cell types of the airway (i.e., tracheo-bronchial) epithelium of lungs from various mammalian species are available (see Chap. 10), reliable and continuously growing cell lines that possess AEC morphology and phenotype are not reported to date. Most studies use cell lines of alveolar epithelial origin for drug absorption studies, while the observations are hard or meaningless to extend to in vivo human situation. 

The situation is, however, different in the alveolar region of the lung where the respiratory gas exchange takes place. Its thin squamous epithelium is covered by the so-called alveolar surface liquid (ASL). Its outermost surface is covered by a mixture of phospholipids and proteins with a low surface tension, also often referred to as lung surfactant. For this surfactant layer only, Scarpelli et al. [74] reported a thickness between 7 and 70 nm in the human lung. For the thickness of an additional water layer in between the apical surface of alveolar epithelial cells and the surfactant film no conclusive data are available. Hence, the total thickness of the complete ASL layer is actually unknown, but is certainly thinner than 1 gm. 

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