Alveolar epithelial membrane

An alternative method which could be used to establish the fraction of protein that actually reaches the alveoli is the so-called co-aerosohzation. If a protein is aerosolized from a solution that also contains another low molecular weight substance (deposition marker), it can be assumed that the fractions of protein and deposition marker reaching the alveoli will be the same. The deposition marker should be a substance with a known alveolar epithelial membrane passage (e.g. tobramycin or a decapeptide) which does not undergo absorption after oral administration. The fraction of the deposition marker that is deposited in the alveoli can be established from plasma (and urine) measurements of the deposition marker. The maximum fraction of protein that can pass the alveolar membrane whl then be known. The ratio between the deposited fraction and the fraction that has been absorbed into the systemic circulation (as can be estabhshed form plasma or urine analysis) will provide an estimation of the protein passage across the alveolar membrane. 

Kinetics of Particle Transport Through the Alveolar Epithelial Membrane... 

Figure 6 Cumulative efficiencies of clearance pathways of HMT rats versus dogs from the epithelial surface either toward ciliated airways or into and through the alveolar epithelial membrane.

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.

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],... 

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. 

Anionic sites on the lumenal surface of pulmonary microvascular endothelium have been shown to bind cationic ferritin in isolated, perfused rat lung studies [196]. The cationic ferritin is taken up by vesicles and discharged into the capillary membrane. Similar anionic sites are also present on alveolar epithelial surfaces [25]. 

Gonzalez RF, Dobbs LG (1998) Purification and analysis of RTI40, a type I alveolar epithelial cell apical membrane protein. Biochim Biophys Acta 1429(1) 208-216... 

Vlahakis NE, Hubmayr RD. Invited review plasma membrane stress failure in alveolar epithelial cells. J Appl Physiol 2000 89 2490-2496. 

The pathogenesis of pulmonary fibrosis is presumably related to initial loss of alveolar type I epithelial cells and endothelial cells. However, the dysregulated repair of pulmonary fibrosis is followed by persistence of inflammation. This is followed by proliferation of type II cells, recruitment and proliferation of endothelial cells and fibroblasts, and deposition of extracellular matrix leading to end-stage alveolar and interstitial fibrosis. These events involve the complex and dynamic interplay between diverse immune effector cells and cellular constituents of the alveolar-capillary membrane and interstitium of the lung. Interaction of these diverse cell populations and the cytokines that they produce culminate in chronic inflammation, angiogenesis, fibroproliferation, and deposition of extracellular matrix. 

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