Alveolar epithelial type I cells

Figure 11.1 Ultrastructure of the human lung alveolar barrier. The tissue specimen is obtained via lung resection surgery. (A) Section through a septal wall of an alveolus. The wall is lined by a thin cellular layer formed by alveolar epithelial type I cells (ATI). Connective tissues (ct) separate ATI cells from the capillary endothelium (en) within which an erythrocyte (er) and granulocyte (gc) can be seen. The minimal distance between the alveolar airspace (ai) and erythrocyte is about 800-900 nm. The endothelial nucleus is denoted as n. (B) Details of the lung alveolar epithelial and endothelial barriers. Numerous caveolae (arrows) are seen in the apical and basal plasma membranes of an ATI cell as well as endothelial cell (en) membranes. Caveolae may partake transport of some solutes (e.g., albumin). (C) ATII cells (ATII) are often localised in the comers of alveoli where septal walls branch off. (D) ATII cells are characterised by numerous multilamellar bodies (mlb) which contain components of surfactant. A mitochondrion is denoted as mi.

Newman GR, Campbell L, von Ruhland C, Jasani B, Gumbleton M (1999) Caveolin and its cellular and subcellular immunolocalisation in lung alveolar epithelium implications for alveolar epithelial type I cell function. Cell Tissue Res 295(1) 111-120... 

BorokZ, Liebler JM, Lubman RL, Foster MJ, Zhou B, Li X, Zabski SM, Kim KJ, Crandall ED (2002) Na transport proteins are expressed by rat alveolar epithelial type I cells. Am J Physiol 282(4) L599-L608... 

Demling N, Ehrhardt C, Kasper M, Laue M, Knels L, Rieber EP (2006) Promotion of cell adherence and spreading a novel function of RAGE, the highly selective differentiation marker of human alveolar epithelial type I cells. Cell Tissue Res 323(3) 475-488... 

Johnson MD, Widdicombe JH, Allen L, Barbry P, Dobbs LG (2002) Alveolar epithelial type I cells contain transport proteins and transport sodium, supporting an active role for type I cells in regulation of lung hquid homeostasis. Proc Natl Acad Sci USA 99(4) 1966-1971... 

McElroy, M.C., and M. Kasper. 2004. The use of alveolar epithelial type I cell-selective markers to investigate lung injury and repair. Eur. Respir. J. 24 664-673. 

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... 

Chen Z, Jin N, Narasaraju T, Chen J, McFarland LR, Scott M, Liu L (2004) Identification of two novel markers for alveolar epithelial type I and II cells. Biochem Biophys Res Commun 319(3) 774—780... 

Chen J, Chen Z, Narasaraju T, Jin N, Liu L (2004) Isolation of highly pure alveolar epithelial type I and type II cells from rat lungs. Lab Invest 84(6) 727-735 Erratum in Lab Invest 85(9) 1181 (2005)... 

Despite the fact that most of the alveolar surface is composited of alveolar epithelium, three primary types of cells are present in the alveoli type I alveolar cells, type II alveolar cells, and alveolar macrophages. Type I alveolar cells are also referred to as squamous pulmonary epithelial cells and are the continuous lining of the alveolar sac. Type II alveolar cells are also referred to as septal cells. Type II alveolar cells secrete the alveolar fluid that is necessary to keep the surface moist and to maintain surface tension of the alveolar fluid surface tension is necessary to keep the alveoli from collapsing. Alveolar fluid is a suitable environment for proteins when compared to the low pH and high protease levels associated with the intestine... 

The lung comprises about 40 different cell types, amongst which type I and type II alveolar epithelial cells are the major types targeted by pulmonary drug delivery systems. Type I cells play an important role in the absorption process of proteins, while type II cells produce surfactant, regulate the immune response, and serve... 

The respiratory alveolar epithelial response to toxic injury can be rapid, resulting in necrosis and subsequently sloughing of the sensitive type I cells. This type of response is seen with exposure to such toxicants as ozone, nitrogen dioxide, and butylated hydroxy toluene. This injury stimulates the proliferation of the more resistant type II cells. This proliferative response typically peaks at 48h after onset of the initial injury to the type I cells. The increase in number of type II cells can be expected to alter the diffusion capacity of the pulmonary region through populating this membrane with these thicker cells. 

The respiratory part of the airways is also shielded by a ciliated epithelium. Along this region the ciliated cells are interspersed by Clara cells which are discussed as progenitor cells of the respiratory epithelium [8,9]. This epithelium has to be separated from the alveolar epithelium, which is a non-ciliated epithelium and formed by alveolar epithelial cells type I and type II. The major surface area of the alveoli is covered by type I cells. Nevertheless, the cuboidal alveolar type II cells represent about 90 % of the alveolar epithelial cells. 

Campbell L, Hollins AJ, Al-Eid A et al (1999) Caveolin-1 expression and caveolae biogenesis during cell transdifferentiation in lung alveolar epithelial primary cultures. Biochem Biophys Res Commun 262(3) 744-751 Danto SI, Zabski SM, Crandall ED (1992) Reactivity of alveolar epithelial cells in primary culture with type I cell monoclonal antibodies. Am J Respir Cell Mol Biol 6(3) 296-306... 

In the separation of alveolar air space and blood circulation, the alveolar epithelium is a more restrictive paracellular barrier than the capillary endothelium. About one-third of the alveolar epithelial cells are type I cells, but these cells make up approximately 95% of the cellular surface area. The remaining two-thirds of the alveolar epithelial cells that comprise the remaining 5% of the cellular surface area are the surfactant-producing cuboidal type II cells.43,45,52 Type I cells have thin cytoplasmic extensions and exhibit a large number of plasmalemmal invaginations called caveolae, which may play a role in macromolecular and protein transport across the blood-air barrier of the lung.44,45,58,59... 

Although interspecies differences can be circumvented through the use of primary cultures of human alveolar epithelial cells, routine use of these cells is limited by availability.58,60 Primary culture of rat type II alveolar epithelial cells is economical and demonstrates high reproducibility, and its phospholipid secretion is similar to that of human type II cells.43 P-gp is expressed in both human and rat type I cells but not in freshly isolated rat type II cells.61 It is assumed that alveolar type II cells are progenitors for regenerating type I cells in vivo, and type II cells in culture lose their cuboidal appearance, lamellar bodies, and microvilli, and the number of surfactant proteins decrease. Monolayers are formed in 5 to 8 days, and the transdifferentiation to type I-like cells is complete within 7-8 days, characterized by the development of attenuations, tighter junctions, and increasing expression of... 

The alveolar epithelium is made up of type I cells or pneumonocytes, which cover most of the alveolar surface. These prevent fluid loss and form the thin gas-exchange barrier. Type II cells are cuboidal and are twice as numerous as the type I cell but cover only about 7% of the surface area. They are metaboli-cally active and responsible for both epithelial cell renewal and synthesizing surfactant, a phospholipid that reduces surface tension forces in the lung (50). Airway epithelium is differentiated by 12 weeks gestation, whereas alveolar epithelium differentiates from 23 weeks of gestation (51). 

Alveolar epithelium consists of three types of cells. Roughly 98 % of the alveolar surface is covered by squamous (type I) epithelial cells, from which thin sheets of cytoplasm extend to cover large areas of surface of even several alveoli (Haies et al. 1981). Type II epithelial cells, though more numerous but compact, occupy only 2 % of the alveolar surface. Type III cells, also called alveolar brush cells, are rare. 

Plutonium particles not phagocytized by alveolar macrophages and removed from the lung are found in type I alveolar epithelial cells, which phagozytize plutonixun particles within a few hours after deposition (Sanders and Adee 1970). These cells appear relatively radioresistant. Fine structural studies of lung exposed to radiation doses up to 13.000 rads from Pu showed no evidence of type I cell detachment or removal (Sanders et al. 1971). 

Cheek JM, Evans MJ, Crandall ED. Type I ceU-Uke morphology in tight alveolar epithelial monolayers. Exp Cell Res 1989 184 375-387. 

In the human, the alveoli are about 200-300 im in diameter and are lined by very thin alveolar epithelial cells. The most prominent of these cells are the type I (also called type A) alveolar epithelial cells, which are only about 0.1 (Am in thickness and cover a wide area. The second most prominent of these cells are the type II cells, which are roughly cuboidal. The type II cells, which are eapable of division, are thought to serve as precursors of type I cells during lung growth or repair. The type II cells also produce surfactant, a surface tensionlowering material that lines the alveoli and reduces the tendency of the very thin-... 

The limited data reporting uptake as a function of time suggest that alveolar epithelial uptake is probably faster than bronchiolar epithelial uptake. Watson and Brain found 5-nm-iron oxide particles within type I cells 1 hr after a 3-hr-inhalation exposure (73). Chrysotile fibers were visible within type I cells at the end of a 1 hr high-level inhalation exposure (55) by 5 hr after exposure, some fibers had been U anslocated to the interstitium. Carbon, latex, and sihca particles have also been shown in type I cells within 24 hr of intratracheal or inhalation exposure (64,76,77). 

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