Respiratory epithelium

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... 

Wilson, R., et al. Measurements of Pseudomonas aeruginosa phenazine pigments in sputum and assessment of their contribution to sputum sol toxicity for respiratory epithelium. Infect. Immun., 56, 2515, 1988. 

ELAM-1 Endothelial leucocyte adhesion molecule-1 ELF Respiratory epithelium lung fluid... 

W. Schurch, H.C. Kaiser and C.C. Harris, The Respiratory Epithelium IV. Histogenesis of Epidermoid Metaplasia and Carcinoma in Situ in the Human, J. Nat 1. Cancer Inst. 61 563-575 (1978). 

Infection of the trachea and bronchi causes hyperemic and edematous mucous membranes and an increase in bronchial secretions. Destruction of respiratory epithelium can range from mild to extensive and may affect bronchial mucociliary function. In addition, the increase in bronchial secretions, which can become thick and tenacious, further impairs mucociliary activity. Recurrent acute respiratory infections may be associated with increased airway hyperreactivity and possibly the pathogenesis of chronic obstructive lung disease. 

Exposure to hexachloroethane vapors can cause irritation to the respiratory system. Acute exposure to 260 ppm hexachloroethane had no apparent effect on the lungs and air passages in rats, but acute exposure to a concentration where particulate hexachloroethane was present in the atmosphere caused lung irritation (Weeks et al. 1979). On the other hand, intermediate-duration exposure to 260 ppm hexachloroethane appeared to cause some irritation of the respiratory epithelium, which may have increased susceptibility to respiratory infection. When exposure ceased, the animals recovered, so there were no histopathological indications of tissue damage after a 12-week recovery period. Lesions of the nasal passages, trachea, and bronchi increased mycoplasma infections mucus in the nasal cavities and decreased oxygen consumption were indicators of respiratory tract irritation from repeated episodes of hexachloroethane exposure. 

There was an increased incidence of a mycoplasma respiratory tract infection in rats exposed to 260 ppm hexachloroethane for 6 weeks but not in rats exposed to lower doses or in other species. This could indicate compromised immune function or a weakened mucosal barrier along the respiratory epithelium. There were no studies identified that evaluated a wide range of immunological parameters. Therefore, there are no reliable LOAELs or NOAELs for this end point. Increases in spleen weights are not classified as LOAELs since they were not accompanied by histopathological changes. 

Excess mucus in the nasal turbinates, irritation of the epithelium, and increased incidence of a mycoplasma respiratory infection were seen in rats with inhalation exposure to 260 ppm for 6 weeks and in pregnant rats with inhalation exposure to 48 ppm for 11 days. Pulmonary irritation was also present in pregnant rats treated with an oral dose of 500 mg/kg/day for 11 days (Weeks et al. 1979). Effects on the respiratory epithelium were not apparent in the tissue of the lungs, nasal cavity, nasal turbinates, larynx, trachea, or bronchi based on histopathological examination (NTP 1977, 1989 Weeks et al. 1979). Exposure to... 

Relative to body weight, humans have a much lower respiratory rate and cardiac output than rodents. These are the two primary determinants of systemic uptake of volatile chemicals. Therefore, at similar nominal concentrations, rodents absorb substantially more cyanide than primates. From a pharmacokinetic view, lower hepatic rhodanese levels in primates will not be significant at high, acute HCN exposures. It should be noted that Barcroft s subject withstood a 1 min and 31 s exposure at approximately 500 to 625 ppm without immediate effects (Barcroft 1931), whereas mice suffer asphyxia during a 2 min exposure at 500 ppm (Matijak-Schaper and Alarie 1982). Compared with rodents, the respiratory tracts of humans and monkeys are more similar in gross anatomy, the amount and distribution of types of respiratory epithelium, and airflow patterns (Barrow 1986 Jones et al. 1996). 

Rylander, R. (1966). Current techniques to measure alterations in the ciliary activity of intact respiratory epithelium. Am. Rev. Respir. Dis. 93 (Suppl) 67-85. 

The volume of the conducting airways that does not contain any respiratory epithelium. This stretches from the nasal cavity to the generation 16 terminal bronchioles (ml). 

An advantage of using the fluid-filled lung is the accuracy of dosimetry and the even distribution of solute throughout the lung. This ensures that permeability is measured across the entire area of the respiratory epithelium. A concern, however, is that the IPL in which the airspaces are flooded with the donor solution may suffer distension of the epithelium leading to increased permeability. 

The highly vascularized respiratory epithelium is composed of five major cell types ciliated cells, nonciliated cells, columnar cells, goblet cells, and basal cells. Low numbers of neurosecretory cells are present in the basement membrane [17]. Approximately 20% of the total number of cells in the lower turbinate area is ciliated with fine projections ( 100 per cell) on the apical cell surface. Cilia are used to transport the mucus toward the nasopharynx. These long (4-6 fxm) and thin projections are mobile and beat with a frequency of 1,000 strokes per min. Ciliated and nonciliated columnar cells are populated with about 300 microvilli per cell, which help in enlarging the surface area. 

McDowell EM, Barrett LA, Glavin F, Harris CC, Trump BF (1978) The respiratory epithelium. I. Human bronchus. J Natl Cancer Inst 61(2) 539-549. 

To determine doses to be used in chronic inhalation studies, F344 rats and B6C3Fi mice of both sexes were exposed to 0, 3, 15, or 75 ppm 1,2-dibromoethane for 13 weeks (NTP 1982 Reznik et al. 1980). Lesions occurred in respiratory turbinates in the dorsal portion of the nasal cavity of rats and mice exposed to 75 ppm. Respiratory epithelium was affected with cytomegaly of basal cells, focal hyperplasia, loss of cilia, and squamous metaplasia. Rats exposed to 15 ppm... 

A study was conducted to examine proliferative nasal epithelial lesions in F344 rats following subchronic inhalation of 1,2-dibromoethane at concentrations of 0, 3, 10, or 40 ppm (Nitschke et al. 1981). The study incorporated serial sacrifices and sacrifices after an 88-89-day postexposure period. Rats in the mid - and high-dose groups had hyperplasia of nasal turbinate epithelium rats at the highest dose also exhibited nonkeratinizing squamous metaplasia of respiratory epithelium of the nasal turbinates. 

Radioactivity from " C-labeled chloroform was detected in the placenta and fetuses of mice shortly after inhalation exposure (Danielsson et al. 1986). In early gestation, accumulation of radioactivity was observed in the embryonic neural tissues, while the respiratory epithelium was more involved in chloroform metabolism in the late fetal period. 

Kotin, P., H. L. Falk, and C. J. McCammon. 111. The experimental induction of pulmonary tumors and changes in respiratory epithelium in C57BL mice following exposure to ozonized gasoline. Cancer 11 473-481, 1958. 

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. ... 

Inhalation of 7 ppm for 6 hours/day caused necrosis and complete erosion of nasal mucosa after 4 days squamous metaplasia of the respiratory epithelium and focal erosion of the olfactory epithelium with evidence of regeneration of some epithelial surface occurred in mice after 9-14 days at this exposure level." Rats and mice exposed to concentrations as low as 4 ppm for 13 weeks had squamous metaplasia, hyperplasia, and inflammation of the nasal mucosa. ... 

In mice exposure to 9 ppm caused a 50% decrease in respiratory rate. Lesions included ulceration and necrosis of the respiratory epithelium and moderate damage to lung tissue. Rats administered, via oral gavage, 10, 20, 40, or 80mg/kg for 10 consecutive days or 32 mg/kg for 90 consecutive days had inflammation, necrosis, acantholysis, hyperkeratosis, and epithelial hyperplasia of the forestomach. Chloropicrin was genotoxic in bacterial test systems."... 

Sneezing, tearing, reddened nose, and lesions of the nasal mucosa were observed in rats exposed at 200ppm for 6.5 hours/day, 5 days/week for 24 weeks. Histopathologic examinations showed squamous metaplasia, suppurative rhinitis, and lymphoid hyperplasia of the respiratory epithelium. 

Rats and mice exposed to 31, 63, or 12 5 ppm 6 hours/day for 16 days developed lesions in the nasal respiratory epithelium and/or olfactory epithelium, and the severity of the lesions generally increased with increasing exposure concentrations. Clinical findings included dyspnea, hypoactivity, and nasal and ocular discharge. At 250ppm all animals died within 4 days. In 2-year inhalation studies at doses of 2, 8, or 32 ppm rats and male mice had increased incidences of nonneoplastic lesions of the nose and increased severity of nephropathy female mice had increased incidences of nonneoplastic lesions of the nose and corneal degeneration. In addition, there was some evidence of carcinogenicity in male rats based on increased incidences of combined neoplasms of the nose and equivocal evidence... 

Oronasal exposure of mice to 2.6ppm led to a 50% decrease in respiratory rate. Mice exposed at 0.3, 1.0, and 2.6ppm 6 hour/day for 4, 9, and 14 days had lesions of the respiratory epithelium including squamous metaplasia, focal necrosis, and keratin exudate that were dose dependent at the lower exposure levels. Lesions persisted 2 weeks after exposure but were decreasing 4 weeks after the end of exposure. No exposure-related lesions were observed in the lungs of exposed mice. 

There was no evidence of carcinogenicity in rats or mice exposed to 0.01, 0.05, or 0.2 ppm for 6 hours/day for 2 years. Pigmentation of the respiratory epithelium occurred in both species, and squamous metaplasia of the laryngeal epithelium occurred in female rats. Geno-toxic assays have been uniformly negative. 

Nasal tumors were induced in rats by inhalation exposure to HMPA for 6-24 months at levels of 50, 100, 400, and 4000 ppb, 6 hours/ day, 5 days week, but not in rats exposed to 10 ppb for 24 months. Most nasal mmors were epidermoid carcinomas and developed from the respiratory epithelium or subepithelial nasal glands, both of which revealed squamous metaplasia or dysplasia in the anterior nasal cavity. 

Two-year inhalation studies (6 hours/day, 5 days/week for 103 weeks) in rodents showed clear evidence of carcinogenicity. Mice exposed at 375 and 750ppm had increased incidences of harderian gland adenomas and carcinomas female mice exposed at 188 and 750 ppm had increased liver neoplasms female rats in the 188 and 375ppm-exposed groups had increased incidences of mammary gland fibroadenomas and carcinomas. Other treatment-related effects were an increase in nasal lesions and degeneration of the respiratory epithelium in mice. 

In rats, 3 500 ppm for 4 hours was considered an approximate lethal concentration. Rats exposed 6 hours/day for 10 days to 0, 75, 250, or 750ppm had dose-dependent degenerative changes in the olfactory and respiratory epithelium. Degeneration of the tracheal mucosa was also observed at the two higher doses. 

Vitamin A is essential for growth and development of cells and tissues. In its active form, retinoic acid (RA), it controls the regular differentiation as a ligand for retinoic acid receptors (RAR, RXR) and is involved in the integration (gap junction formation) of cell formations (Biesalski, 1996 Biesalski et al, 1999). Vitamin A plays a substantial role, especially in the respiratory epithelium and the lung. During moderate vitamin A deficiency, the incidence for diseases of the respiratory tract is considerably increased and repeated respiratory infections can be influenced therapeutically by a moderate vitamin A supplementation (Biesalski et ah, 2001 Greenberg et ah, 1997 John et ah, 1997). 

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