Respiratory epithelial cells

The physiological role of the ICOR is not clear and may be heterogeneous in the various tissues. In the thick ascending limb of the loop of Henle this channel appears to serve as the exit for CP at the basal cell pole [16,65,66], This conductive mechanism, therefore, is required for the reabsorption of Na and CP by this segment of the nephron [16]. In the rectal gland of Squalus acanthias a very similar channel is utilized for Na" and CP secretion. In these latter cells the CP-channel is present in the luminal membrane and is controlled by cytosolic cAMP [15,56,71]. It has been claimed that this kind of channel is also responsible for the secretion of CP in the colonic crypt cell, in colonic carcinoma cells and in respiratory epithelial cells [17,19,20,22]. Recent data have cast some doubt on this concept ... 

CP-channels with even smaller conductance have been described for the lacrimal and other exocrine glands [76,77]. These channels have a conductance of 1-2 pS. Unlike the ICOR-channel they appear to be blocked by millimolar concentrations of furosemide [77]. Most recent and only partially published data from my own laboratory obtained with the above modified nystatin technique [50,133,134] indicate that the respiratory epithelial cells and colonic carcinoma cells possess these types of small CP channels, and that these channels are involved in hormonal regulation of CP-conductance (cf. section 5). These CP-channels are regulated by cytosolic Ca. Hormonally induced increases in cytosolic Ca lead to an abrupt increase in the probability of these small CP-channels being open, yet they have no effect on the ICOR-channel. Data of this kind reinforce that the physiological importance of these small CP-channels may have been grossly underestimated. 

Belcher CE et al. The transcriptional responses of respiratory epithelial cells to BordeteUa pertussis reveal host defensive and pathogen counter-defensive strategies. Proc Natl Acad Sci USA 2000 97 13847-13852. 

Curiel DT, Agarwal S, Romer N, Wagner E, Cotten M, Bimstiel ML, Boucher RC (1992) Gene transfer to respiratory epithelial cells via the receptor-mediated endocytosis pathway. Am J Resp Cell Mol Biol 6 247-252... 

The cystic fibrosis (cf) gene was first identified in 1989. It codes for CFTR, a 170 kDa protein that serves as a chloride channel in epithelial cells. Inheritance of a mutant cftr gene from both parents results in the cystic fibrosis phenotype. While various organs are affected, the most severely affected are the respiratory epithelial cells. These cells have, unsurprisingly, become the... 

N. R. Mathias, F. Yamashita, and V. H. Lee. Respiratory epithelial cell culture models for evaluation of ion and drug transport. Adv Drug Deliv Rev 22 215-249 (1996). 

Calu-3 (American type culture collection ATCC HTB-55) is a human bronchial epithelial cell line derived from an adenocarcinoma of the lung [59], This cell line has been shown to exhibit serous cell properties and form confluent monolayers of mixed cell phenotypes, including ciliated and secretory cell types [60], but the cilia are formed very irregularly and seem to disappear with increasing passage number (unpublished observations, C.E. and B.F.). Calu-3 cells have shown utility as a model to examine transport [61-63] and metabolism in human bronchial epithelial cells for many therapeutic compounds [64], Furthermore, they have been used in a number of particlecell interaction studies [65-67], The interactions between respiratory epithelial cells and particulates are discussed more in detail in Chap. 19. 

Forbes B, Ehrhardt C (2005) Human respiratory epithelial cell culture for drug delivery applications. Eur J Pharm Biopharm 60(2) 193-205. 

Vitamin C (VC, L-ascorbic acid) is known to be essential for many enzymatic reactions. Sodium-dependent VC transporters (SVCT), SVCT1 and SVCT2, were recently identified and reported to be localised in the apical cell membrane of AECs in the lung of adult rats. These results suggest that SVCT proteins could transport the reduced form of VC from the airway/alveolar surface liquid into respiratory epithelial cells [106],... 

Duncan JE, Whitsett JA, Horowitz AD (1997) Pulmonary surfactant inhibits cationic liposome-mediated gene delivery to respiratory epithelial cells in vitro. Hum Gene Ther 8(4) 431-438... 

Wikenheiser KA, Vorbroker DK, Rice WR, Clark JC, Bachurski CJ, Oie HK, Whitsett JA (1993) Production of immortalized distal respiratory epithelial cell lines from surfactant protein C/simian virus 40 large tumor antigen transgenic mice. Proc Natl Acad Sci USA 90(23) 11029-11033... 

Barthelson, R., Mobasseri, A., Zopf, D., and Simon, P. (1998). Adherence of Streptococcus pneumoniae to respiratory epithelial cells is inhibited by sialylated oligosaccharides. Infect. Immun. 66,1439-1444. 

Hanski, E., Horwitz, P. A., and Caparon, M. G. (1992). Expression of protein F, the fibronectin-binding protein of Streptococcus pyrogenes JRS4, in heterologous streptococcal and enterococcal strains promotes their adherence to respiratory epithelial cells. Infect. Immun. 60, 5119-5125. 

The influenza vaccine induces the production of antibodies. These antibodies block the attachment of H5N1 virus to the human respiratory epithelial cells. 

Barrett, J.C., Gray, T.E., Mass, M.J., and Thomassen, D.G. (1982). A quantitative, clonal assay for carcinogen-induced alterations of respiratory epithelial cells in culture, in Application of Short-term Bioassays in the Analysis of Complex Environmental Mixtures, Waters, M. and Sandu, S., Eds. (Plenum Press, New Y>rk). 

Yoo, C.G., Lee, S., Lee, C.T., Kim, Y.W., Han, S.K. and Shim, Y.S. (2000) Anti-inflammatory effect of heat shock protein induction is related to stabilization of IkappaB alpha through preventing IkappaB kinase activation in respiratory epithelial cells. J. Immunol., 164, 5416-5423. 

Salem LB, Bosquillon C, Dailey LA et al (2009) Sparing methylation of beta]-cyclodextrin mitigates cytotoxicity and permeability induction in respiratory epithelial cell layers in vitro. J Control Release 136(2) 110—116... 

Bennett, M. J., Nantz, M. H., Balasubramaniam, R. P., et al. Cholesterol enhances cationic liposome-mediated DNA transfection of human respiratory epithelial cells. Biosci. Rep. 15(l) 47-53. 1995. 

Wheeler, D. S., Catravas, J. D., Odoms, K., Denenberg, A., Malhotra, V, Wong, H. R. (2004). Epigallocatechin-3-gallate, a green tea-derived polyphenol, inhibits lL-1 beta-dependent proin-flammatory signal transduction in cultured respiratory epithelial cells. J. Nutr., 134,1039-1044. 

Gao, X., Ray, R., Xiao, Y., Barker, P.E., Ray, P. (2007). Inhibition of sulfur mustard-induced c dotoxicity and inflammation by the macrolide antibiotic roxithromycin in human respiratory epithelial cells. BMC Cell Biol. 8 17. 

Correction of the chloride channel defect in cells explanted from CF patients by the introduction of the normal CFTR cDNA suggests that gene therapy may be beneficial. It may be sufficient to deliver the normal cDNA just to the respiratory epithelial cells. A number of strategies for gene therapy by using viral vectors and other delivery methods are under development and are being tested (Collins, 1992). These approaches are discussed in detail in Chapter 6. 

Haghi M, Young PM, Traini D et al (2010) Time- and passage-dependent characteristics of a Calu-3 respiratory epithelial cell model. Drug Dev Ind Pharm 36(10) 1207-1214... 

Chevillard, M., Lainee, P., Robineau, P., and Puchelle, E. (1992). Toxic effects of sulfur mustards on respiratory epithelial cells in culture. Cell Biol Toxicol 8, 171-81. 

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