Cells Clara

Nonciliated bronchiolar epithelial cells were first described by Koelliker (1881), but the earhest detailed study was that of Clara (1937), after whom they were named by Policard (1955). 

Have-Opbroek (1986), Forkert and Troughton (1987), Moussa and Forkert (1992) 

In the light microscope, Clara cells appear columnar, have a deeply invaginated central nucleus, 

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Clara cell protein (CC10, phospholipase A2inhibitor) Inducible cyclooxygenase (COX-2)... 

B6C3F1) dilation of endoplasmic reticulum in Clara cells) 1991... 

Odum J, Foster JR, Green T. 1992. A mechanism for the development of Clara cell lesions in the mouse lung after exposure to trichloroethylene. Chem Biol Interact 83 135-153. 

Papillary tumors, apparently derived from Clara cells, in the bronchiolar epithelium have been reported in a group of 12 New Zealand rabbits exposed to 3,000 ppm -hexane for 8 hours a day, 5 days a week for 24 weeks (Lungarella et al. 1984), but the incidence was not reported. 

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.

Boers JE, Ambergen AW, Thunnissen FB (1999) Number and proliferation of Clara cells in normal human airway epithelium. Am J Respir Crit Care Med 159(5 Pt 1) 1585—1591. 

Oreffo VI, Morgan A, Richards RJ (1990) Isolation of Clara cells from the mouse lung. Environ Health Perspect 85 51-64. 

Zhang L, Whitsett JA, Stripp BR (1997) Regulation of Clara cell secretory protein gene transcription by thyroid transcription factor-1. Biochim Biophys Acta 1350(3) 359-367... 

After acute mild insult the nonciliated cells proliferate and the epithelium regenerates to normal. In the airways, nonciliated basal cells are the main proliferating population. In the bronchioles, the Clara cell is the main precursor cell for regeneration. Because of the delicate nature of the respiratory tract epithelium and the close proximity of subepithelial blood vessels, an inflammatory response occurs to all but the mildest form of injury. Many lesions are therefore diagnosed as rhinitis, tracheitis, and bronchiolitis and qualified as acute, subacute, and chronic depending on the stage of the response. 

In animals, acute oral exposure to doses of 4,000 mg/kg has been observed to cause respiratory edema, atelectasis and hemorrhage (Gould and Smuckler 1971). This is accompanied by marked disruption of subcellular structure in most pulmonary cell types, including granular pneumocytes, capillary endothelial cells and Clara cells (Boyd et al. 1980 Gould and Smuckler 1971 Hollinger 1982). It has been shown that Clara cells were most severely injured because they are the most active in metabolic activation of carbon tetrachloride. Injury to capillary endothelial cells is dose-... 

Boyd MR, Statham CN, Longo NS. 1980. The pulmonary Clara cell as a target for toxic chemicals requiring metabolic activation studies with carbon tetrachloride. J Pharmacol Exp Ther212 109-114. 

Yano T, Shibagaki T, Kitamura H, et al. 1988. The mechanism of carbon tetrachloride induced pulmonary clara cell damage biochemical and morphologic studies. Res Commun Chem Pathol Pharmacol 62 483-493. 

White, J. F. Foley, R. R. Maronpot, and NT108 M. W. Anderson. Role of Clara cells and type II cells in the development of pulmonary tumors in rats and mice following exposure to a tobacco-specific nitrosamine. Exp Lung Res 1991 ... 

Chronotropic. Affecting the time or rate, as the rate of contraction of the heart. Clara cells. Unciliated cells occurring at the boundary where alveolar ducts branch from the bronchioles. 

Bom, S.L., Rodriguez, P.A., Eddy, C.L. Lehman-McKeeman, L.D. (1997) Synthesis and reactivity of coumarin 3,4-epoxide. DrugMetab. Disp., 25, 1318-1323 Bom, S.L., fix, A.S., Caudill, D. Lehman-McKeeman, L.D. (1998) Selective Clara cell injury in mouse lung following acute administration of coumarin. Toxicol, appl. Pharmacol., 151, 45-56... 

Kauffman, S.L., Alexander, L., and Saas, L. (1979). Histological and ultrastructural features of the Clara cell adenoma of the mouse lung, Lab. Invest. 40,708. 

Ploer, C.G. (1983). Comparative morphologic features of bronchiolar epithelial cells The Clara cell. Am. Rev.Resp. Dis., 128, s37-s41. 

The elucidation of the mechanism has revealed that this specificity is due to a requirement for metabolic activation for which the Clara cell is particularly suited. Thus, early studies using radiolabeled 4-ipomeanol found that the compound was localized particularly in the lungs (when expressed as nmol g-1 wet weight of tissue), and was covalently bound to lung protein (Fig. 7.38). This binding was five times that seen in the liver. Furthermore, autoradiography revealed that the radiolabeled 4-ipomeanol was bound to the Clara cells,... 

Inhibitors of the microsomal enzymes decreased the covalent binding and the Clara cell necrosis and increased the LD50, even though the blood and pulmonary levels of ipomeanol... 

The susceptibility of the lung is probably due to the location of the CYP4B1, which is particularly expressed in Clara cells. An additional reason could be the relative lack of protection such as lower levels of GSH than the liver, for instance. 

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