Respiratory epithelial function

In respiratory epithelial (RE) cells the Cl -conductance was attributed to the ICOR channel. In fact, it was reported by Frizzell et al. and Welsh s laboratories that catecholamines increased the incidence of ICOR channels in cell attached patches of normal RE cells but failed to do so in CF cells [110,111], Later both laboratories presented data on excised membrane patches of RE cells in which the protein kinase A which was added to the cytosolic side produced ICOR channel activity in the normal cells but not in the CF tissues [19,20]. This finding was reproduced by Guggino and coworkers [22] for RE cells and by others for lymphocytes [46]. Protein kinase C at physiological Ca -activities had a comparable effect in normal cells but also failed to function in CF cells [22,112]. 

Eosinophil infiltration is a major feature of asthma and allergic reactions [203], These cells are not abundant during the acute phase of the response, but increase in number and account for 10-80% of the total cell infiltrate during the late phase. Furthermore, major basic protein (MBP), which is released from eosinophil granules, causes respiratory epithelial damage [204]. Since PAF is a potent activator of eosinophil functions [205], BN 52021 may interfere with the late phase response. 

ENaC is located in the apical membrane of polarized epithelial cells where it mediates Na+ transport across tight epithelia [3], The most important tight epithelia expressing ENaC include the distal nephron of the kidney, the respiratory epithelium, and the distal colon. The basic function of ENaC in polarized epithelial cells is to allow vectorial transcellular transport of Na+ ions. This transepithelial Na+ transport through a cell involves... 

In experimental animals the respiratory system is a primary target of acrolein exposure after inhalation, and there is an inverse relationship between the exposure concentration and the time it takes for death to occur." Inhalation LCso values of 327ppm for 10 minutes and 130ppm for 30 minutes have been reported in rats." Of 57 male rats, 32 died after exposure to 4 ppm for 6 hours/day for up to 62 days. Desquamation of the respiratory epithelium followed by airway occlusion and asphyxiation is the primary mechanism for acrolein-induced mortality in animals." Sublethal acrolein exposure in mice at 3 and 6 ppm suppressed pulmonary antibacterial defense mechanisms. A combination of epithelial cell injury and inhibition of macrophage function may be responsible for acrolein-induced suppression of pulmonary host defense. ... 

In some cases, cells in a persistently stressful environment may be replaced by a cell type that is better able to withstand the harsh environment. Replacement of an adult cell type by another adult cell type is known as metaplasia and is usually a reversible change. Perhaps the best-known example of metaplasia is the replacement of the normally tall (columnar), ciliated epithelial cells in the respiratory tract of cigarette smokers by layers of relatively flattened (squamous) epithelial cells. While the squamous epithelial cells are somewhat tougher than the columnar cells, important functions such as mucus secretion are lost. In addition, the continued stresses that induce metaplasia may lead to neoplastic transformation. 

---