Type I cells

Williams MC. Alveolar type I cells molecular phenotype and development. Annu Rev Physiol 2003 65 669-695. 

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.

ATII cells, when plated on permeable supports or plastics under appropriate culture conditions, acquire features of type I cell-like phenotype and morphology [30, 57, 80], Although isolation of ATI pneumocytes from rat lungs has recently been reported with some success [28, 48, 81], development of confluent ATI cell monolayer with electrically tight characteristics has not been reported yet. It should be noted that unlike many other cells in primary culture, AEC exhibits generally a very limited proliferation profile and is therefore not suitable for passaging. Thus, a new preparation of cells has to be used for each data set, which drives the costs up tremendously, and a reliable normalisation scheme of data observed from each set of cell preparations is needed. 

Dahlin K, Mager EM, Allen L, Tigue Z, Goodglick L, Wadehra M, Dobbs L (2004) Identification of genes differentially expressed in rat alveolar type I cells. Am J Respir Cell Mol Biol 31(3) 309-316... 

Rishi AK, Joyce-Brady M, Fisher J, Dobbs LG, Floras J, VanderSpek J, Brody JS, Williams MC (1995) Cloning, characterization, and development expression of a rat lung alveolar type I cell gene in embryonic endodermal and neural derivatives. Dev Biol 167(1) 294-306... 

Williams MC, Cao Y, Hinds A, Rishsi AK, Wetterwald A (1996) T1 alpha protein is developmentally regulated and expressed by alveolar type I cells, choroid plexus, and ciliary epithelia of adult rats. Am J Respir Cell Mol Biol 14(6) 577-585... 

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... 

Uchida T, Shirasawa M, Ware LB, Kojima K, Hata Y, Makita K, Mednick G, Matthay ZA, Matthay MA (2006) Receptor for advanced glycation end-products is a marker of type I cell injury in acute lung injury. Am J Respir Crit Care Med 173(9) 1008-1015... 

Dobbs LG, Gonzalez RF, Allen L, Froh DK (1999) HTI56, an integral membrane protein specific to human alveolar type I cells. J Histochem Cytochem 47 129-137... 

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... 

The alveolar epithelium consists of so-called Type I and Type II cells. Type I cells cover over 90% of the alveolar surface, have a large surface, and are thin. Type II cells are larger in numbers but are small. Therefore, they cover only about 7% of the surface of the alveoli. Type II cells produce the phospholipids that make up the surfactant layer. 

The isolation and characterization of alveolar Type II cells which transform into alveolar Type I cells has been described, as weh as a monolayer culture of alveolar Type I cells [35,36]. 

T e II cells (granular pneumonocytes) are distributed throughout the alveoli between T e I cells. Although they are more numerous than T e I cells, they are cuboidal in shape and occupy far less of the alveolar surface area. The prime function of this cell is the production of pulmonary surfactant, and it is generally less susceptible to injury than the Type I cell. 

Most direct toxins entering the alveoli primarily affect Type I cells and their associated capillary endothelial cells. After acute injury, the epithelium and/or underlying capillary endothelial cells may swell and disrupt, distort, or lose their connections with others, leaving large areas of basement membrane uncovered. This allows fluid to move into the alveolar lumen from capillaries, with subsequent pulmonary edema. 

The sequel to acute injury depends on the potency and concentration of the toxic agent and the duration of exposure. Potent gases produce a severe vascular reaction and alveolar flooding. The fluid prevents gaseous exchange, and death of the human or animal ensues. After acute mild nonlethal damage, excess fluid is removed and the resistant Type II cells proliferate and reline the alveoli. The cells subsequently differentiate into Type I cells. 

N02 is a relatively insoluble deep lung irritant capable of producing pulmonary edema. The type I cells of the alveoli appear to be the cells chiefly affected on acute exposure. At higher exposure, both type I and type II alveolar cells are damaged. Exposure to 25 ppm of N02 is irritating to some individuals 50 ppm is moderately irritating to the eyes and nose. Exposure... 

In addition to these molecules, naturally occurring neutralizing autoantibodies of IgG type to IL-la have been identified. These have been detected in serum isolated from human donors. [35,36]. These antibodies bind to both proIL-la and 17-kDa IL-la [37] and completely prevent the binding of IL-la to type-I cell surface receptors [38]. Patients with autoimmune diseases have higher populations of these antibodies [39]. 

Barriers to pulmonary absorption of proteins and peptides include respiratory mucus, mucociliary clearance, pulmonary enzymes/proteases, alveolar lining layer, alveolar epithelium, basement membrane, macrophages and other cells [3, 18]. The molecular weight cutoff of tight junctions for alveolar type I cells is 0.6 nm, while endothelial junctions allow the passage of larger molecules (4-6 nm). In order to reach the bloodstream in the endothelial vasculature, proteins and peptides must cross this alveolar epithelium, the capillary endothelium, and the intervening extracellular matrix. 

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... 

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 pulmonary alveolar epithelium is comprised of two morphologically distinct cells, type I and type II cells. Type I cells are extremely large, squamous cells that make up 95% of the alveolar surface. Type II cells are smaller cuboidal cells that secrete and recycle surfactant and cover the remaining 5% of the alveolar surface. Mechanical distention of fetal lung tissue has been shown to stimulate expression of the type I cell phenotype and inhibit expression of the type II phenotype. Lumenal mechanical stim-... 

Type I cells comprise 8-11% of the structural cells found in the alveolar region and yet cover 90-95% of the alveolar surface. Their major function is to allow gases to equilibrate across the air-blood barrier and to prevent leakage of fluids across the alveolar wall into the lumen. The type I epithelium is particularly sensitive to damage from a variety of inhaled toxicants due to their large surface area. Moreover, their repair capacity is limited because they have few organelles associated with energy production and macromolecular synthesis. 

Capillary endothelial cells comprise 30-42% of cells in the alveolar region and comprise the walls of the extensive network of blood capillaries in the lung parenchyma. The endothelium forms a continuous, attenuated cell layer that transports respiratory gases, water, and solutes. However, it also forms a barrier to the leakage of excess water and macromolecules into the pulmonary interstitial space. Pulmonary endothelial cells, like type I cells, are vulnerable to injury from inhaled substances and substances in the systemic circulation. Injury to the endothelium results in fluid and protein leakage into the pulmonary interstitium and alveolar spaces, resulting in pulmonary edema. 

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