Bronchial epithelium cells

All cells produce movement internally, and many are capable of motility or of changing shape. In some, movement is related to the function of individual cells, as in the migratory and engulfing movements of phagocytic cells or the swimming movements of sperm cells. In other cases, cells generate movement as one aspect of tissue function, as in the ciliary transport of mucus by the bronchial epithelium. Cells specialized for changing the dimensions or shape of anatomical structures or for movement of body parts with respect to each other are called muscle cells. 

It is reasonable to conclude that dose to cells throughout the bronchial tree may contribute to the risk of lung cancer and not just the dose received by certain cells in the large central airways. It is probably also appropriate to evaluate the dose absorbed by cells throughout the depth of bronchial epithelium, i.e. the mean dose,... 

The dose received by cells in the bronchial epithelium from decay of the alpha-emitting radon daughters at the airway surface decreases rapidly with depth in tissue. The data available show that the thickness of bronchial epithelium is highly variable (Gastineau et al., 1972) but the distribution of values can be formalised (Wise,... 

It is possible to infer cross population risk if the detailed dose delivered to target cells in bronchial epithelium is calculated for the various population groups since it is the dose which confers the risk. 

Current lung dosimetry models are based on the assumption that basal cells of the bronchial epithelium are the critical target cells for malignant transformation and that the alpha dose to these cells is the relevant radiation dose. 

Lips KS, Volk C, Schmitt BM, Pfeil U, Arndt P, Miska D, Ermert L, Kummer W, Koepsell FI (2005) Polyspecific cation transporters mediate luminal release of acetylcholine from bronchial epithelium. Am J Respir Cell Mol Biol 33 79-88. 

Figure 10.1 Typical tracheo-bronchial and bronchiolar epithelia showing the major cell types. The tracheo-bronchial epithelium showing the pseudostratified nature of the columnar epithelium, principally composed of ciliated cells (C), interspersed with goblet cells (G), brush cells (Br), serous cells (S), Kulchitsky s cells (K) and basal cells (B). The bronchiolar epithelium showing the cuboidal nature of the epithelium, principally composed of ciliated cells (C), Clara cells (Cl) and infrequent basal cells. Muc = mucus Ci = cilia N = nucleus Sec = secretory granules.

While all the aforementioned cell types form the epithelial surface of the airways, basal cells reside deep in the tracheo-bronchial epithelium and are not directly in contact with the airway lumen. Basal cells are considered as the stem cell or progenitor cell of the bronchial epithelium and are pyramidal in shape with a low cytoplasmic/nuclear volume ratio [8, 15-17],... 

Lung resistance protein Lung resistance protein (LRP) is expressed in normal human bronchial epithelium (NHBE) as well as in other tissues potentially exposed to toxins [104], LRP was reported to be expressed in both Calu-3 cells [105] and 16HBE14o- model [70], However, the role of LRP in different cellular locations is not clear to date. 

A variety of cell culture systems for the modelling of the tracheo-bronchial epithelium are available. These include primary cultures and cell lines of human and animal origins, plus airway cells with characteristics of lung disease such as CF. The advantages and limitations of using a simple culture system compared to one that recreates to a greater extent the epithelial structure and function in vitro should be considered according to the pre-clinical application required. However, this choice is complicated by the lack of comparative data, both between the different cell systems and for in vitro-in vivo correlation, upon which to base such decisions. 

Breuer R, Zajicek G, Christensen TG, Lucey EC, Snider GL (1990) Cell kinetics of normal adult hamster bronchial epithelium in the steady state. Am J Respir Cell Mol Biol 2(1) 51—58. 

Ehrhardt C, Collnot EM, Baldes C, Becker U, Laue M, Kim KJ, Lehr CM (2006) Towards an in vitro model of cystic fibrosis small airway epithelium Characterisation of the human bronchial epithelial cell line CFBE41o-. Cell Tissue Res 323(3) 405-415. 

While morphological features of AECs are well characterised, only few molecules have been identified which can be used as clear signatures for the respective cell type. These markers are summarised in the following paragraphs. The best marker for AT II cells is SP-C, which is exclusively expressed in this cell type. All other SP, such as SP-D, are also expressed in cells of the bronchial epithelium or even other epithelial cells of the body [16]. 

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. 

Alternatively the membrane passage of human airway epithehal ceh lines can be studied in vitro. A number of bronchial epithehal ceh hnes is available, such as the 16HBE14o- and Calu-3 cell hnes. These ceh hnes can be installed in diffusion chambers to measure transport rates [34]. A major disadvantage of the currently used cell hnes is that they provide information about bronchial epithehal transport only. Since bronchial epithelium is very different from alveolar epithehum, the information from these in vitro studies is of limited value for the prediction of the bioavahabihty of pulmonary administered proteins. 

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