The Clara Cell

Öz

Clara cells firstly identified as a distinct cell type by Kolliker in 1881 are non-ciliated secretory cells located in the small airways. These cells can be easily identified by their distinct dome-shaped morphology and numerous secretory granules among the other epithelial cells. The distribution of Clara cells throughout the respiratory system is in a species-specific manner. These cells have several lung protective functions. Clara cells, basically function in lung homeostasis, play roles in xenobiotic metabolism and immune system regulation. In humans, many forms of lung cancer originate from Clara cells. The aim of this review was to give information about morphological and function features of the Clara cells. Key words: Clara Cell; Bronchiol; Lung.

Anahtar Kelimeler

• Clara Cell; Bronchiol; Lung.

Clara Hücresi

Öz

İlk kez 1881 yılında Kolliker tarafından farklı bir hücre tipi olarak tanımlanan Clara hücreleri küçük hava yollarında bulunan, sil içermeyen, sekretuar hücrelerdir. Diğer epitel hücreleri arasında kubbe biçimli morfolojileri ve bol sekretuar granülleri ile kolay tanınırlar. Clara hücrelerinin respiratuar sistemdeki dağılımı türe özgü farklılıklar gösterir. Bu hücreler akciğeri koruyucu çeşitli fonksiyonlara sahiptir. Temel olarak akciğer homeostazının sağlanmasında görev alan Clara hücreleri, ksenobiyotik metabolizmasında ve immun sistemin regülasyonununda da rol alırlar. İnsanlarda akciğer kanserinin pek çok formu Clara hücrelerinden kaynaklanmaktadır. Bu derlemenin amacı; Clara hücrelerinin morfolojik ve fonksiyonal özellikleri hakkında bilgi vermektir. Anahtar kelimeler: Clara Hücresi; Bronşiyol; Akciğer.

Anahtar Kelimeler

• Clara Hücresi; Bronşiyol; Akciğer.

Kaynakça

1. ReynoldsSD, Malkinson AM. Clara Cell Progenitor for the Bronchiolar Epithelium. Int J of Biochem Cell Biol 2010; 42: 1-4. DOI: 10.1016/j.biocel.2009.09.002
2. Chang A, Ramsay P, Zhao B, et al. Physiological Regulation of Uteroglobin/CCSP Expression. Ann N Y Acad Sci 2000; 923: 181-92. DOI: 10.1111/j.1749- 6632.2000.tb05529.x
3. Matulionis DH, Parks HF. Ultrastructural Morphology of the Normal Nasal Respiratory Epithelium of the Mouse. Anatom Rec 1973; 175: 68-84. DOI: 10.1002/ar.1091760105
4. Souma T. The Distribution and Surface Ultrastructure of Airway Epithelial Cells in the Rat Lung: A Scanning Electron Microscopic Study. Arch of Histol Japan 1987; 50: 419-36.
5. Bishop AE. Pulmonary Epithelial Stem Cells. Cell Prolif 2004; 37: 89-96.
6. Hackett BP, Gitlin JD. Cell-Specific Expression of A Clara Cell Secretory Protein-Human Growth Hormone Gene in the Bronchiolar Epithelium of Transgenic Mice. Proc Nati Acad Sci 1992; 89: 9079-83. DOI: 10.1073/pnas.89.19.9079
7. Sadler TW. Langman Medikal Embriyoloji, 9. baskı,
8. Ankara, 2005; sayfa 272.

9. Mc Donald JA. Lung Growth and Development. Informa Healthcare 1997; 59-61.
10. Coraux C, Nawrocki-raby B, Hinnrasky J, et. al. Embriyonic Stem Cells Generate Airway Epithelial Tissue. Am J Respir Cell Mol Biol 2005; 32: 87-92. DOI: 10.1165/rcmb.2004-0079RC.
11. Esrefoglu M. Genel ve Özel Histoloji; 1. basım, Malatya: 2009; sayfa.: 144.
12. Atkinson JJ, Adair-Kirk TL, Kelley DG, et al. Clara Cell Adhesion and Migration to Extracellular Matrix. Respir Res 2008; 9:1. DOI: 10.1186/1465-9921-9-1
13. Elizur A, Adair-Kirk TL, Kelley DG, et. al. Clara Cells Impact the Pulmonary Innate Immune Response to LPS. Am J Physiol Lung Cell Mol Physiol 2007; 293: L383- L392. DOI: 10.1152/ajplung 00024.2007
14. Massaro GD, Paris M, Thet LA. In Vivo Regulation of Secretion of Bronchiolar Clara Cells in Rats. J, Clin Invest 1979; 63: 167-72. DOI: 10.1172/JCI109285.
15. Pack RJ, Al-Ugaily LH, Morris G. The Cells of the Tracheobronchial Epithelium of the Mouse: A Quantitative Light and Electron Microscope Study. J, Anat 1981; 132: 71-84.
16. Cutz E, Conen PE. Ultrastructure and Cytochemistry of Clara Cells. Am J of Pathol 1971; 62: 1.
17. Wang NS, Huang SN, Sheldon H, Thurlbeck WM. Ultrastructural Changes of Clara and Type 2 Alveolar Cells in Adrenalin-induced Pulmonary Edema in Mice. Am J of Pathol 1971; 62: 2.
18. Smith P, Heath D, Moosavı H. The Clara Cell. Thorax 1974; 29: 147-63. DOI:10.1136/thx.29.2.147
19. Lumsden AB, Mclean A, Lamb D. Goblet and Clara cells of Human Distal Airways: Evidence for Smoking Induced Changes in Their Numbers. Thorax 1984; 39: 844-9. DOI:10.1136/thx.39.11.844
20. Oreffo VC, Morgan A, Richards RJ. Isolation of Clara Cells from the Mouse Lung. Environ Health Perspectives 1990; 85: 51-64.
21. Devereux TR. Alveolar Type 2 and Clara Cells. Isolation and Xenobiotic Metabolism. Environ Health Perspectives 1984; 56: 95-101.
22. Van Haute L, De Block G, Liebaers I, et al. Generation of Lung Epithelial-Like Tissue from Human Embryonic Stem Cells. Resp Res 2009; 10:105. DOI:10.1186/1465- 9921-10-105
23. Yoneda K. Ultrastructural Localization of Phospholipases in the Clara Cell of the Rat Bronchiole. Am J Pathol 1978; 93:3.
24. Yao XL, Ikezono T, Cowan M, et al. Interferon-Gamma Stimulates Human Clara Cell Secretory Protein Production by Human Airway Epithelial Cells. Am J Physiol Lung Cell Mol Physiol 1998; 274: 864-9.
25. Broeckaert F, Bernard A. Clara Cell Secretory Protein (CC16): Characteristics and Perspectives As Lung Peripheral Biomarker. Clin Exp Allergy 2000; 30: 469-75. DOI: 10.1046/j.1365-2222.2000.00760.x
26. Janssen R, Sato H, Grutters JC, et al. Clara Cell 10 Adenine-38-Guanine Polymorphism and Sarcoidosis Susceptibility in Dutch and Japanese Subjects. Am J Respir Crit Care Med 2004; 170: 1185-87. DOI: 10.1164/rccm.200404-481OC
27. Singh G, Singh J, Katyal SL, et al. Isolation, Cellular Localization, Identification and Characterization of Human Clara Cell-Spesific 10 Kda Protein. J Histochem Cytochem 1988; 36: 73-80.
28. Hermans C, Petrek M, Kolek V, et al. Serum Clara Cell Protein (CC16), A Marker of the Integrity of the Air- Blood Barrier in Sarcoidosis. Eur Respir J 2001; 18: 507- 14.
29. Helleday R, Segerstedt B, Forsberg B, et al. Exploring the Time Dependence of Serum Clara Cell Protein as A Biomarker of Pulmonary Injury in Humans. Chest 2006; 130:672-5. DOI: 10.1378/chest.130.3.672
30. Blomberg A, Mudway I, Svensson M, et al. Clara Cell protein as A Biomarker for Ozone-Induced Lung Injury in Humans. Eur Respir J 2003; 22: 883-8. DOI: 10.1183/09031936.03.00048203
31. Bernard A, Thielemans N, Lauwerys R, et al. Clara Cell Protein in Human Amniotic Fluid: A Potential Marker of Fetal Lung Growth. Pediatr Res 1994; 36: 771-5. DOI:10.1203/00006450-199412000-00015
32. Ashwood ER, Palmer SE, Lenke RR. Rapid Fetal Lung Maturity Testing: Commercial Versus NBD- Phosphatidylcholine Assay. Obstet Gynecol 1992; 80: 1048-53.
33. Andres M, Alfred B, Alfredo M, G, et al. Amniotic Fluid Clara Cell Protein Concentration in Normal Pregnancy, A Marker of Fetal Airway Growth or Fetal Lung Maturation? J of Perinatol 2001; 21:516-20.
34. Hermans C, Knoops B, Wiedig M, et al. Clara Cell Protein as A Marker of Clara Cell Damage and Bronchoalveolar Blood Barrier Permeability. Eur Respir J 1999; 13: 1014-21.
35. Nomori H, Horio H, Takagi M, et al. Clara Cell Protein Correlation with Hyperlipidemia. Chest 1996; 110:680-4. DOI: 10.1378/chest.110.3.680
36. Massaro GD, Fischman CM, Chiang M, et al. Regulation of Secretion in Clara Cells: Studies Using the Isolated Perfused Rat Lung. J. Clin. Invest 1981; 67: 345-51.DOI: 10.1172/JCI110041
37. Newton DA, Rao KMK, Dluhy RA, Baatz JE. Hemoglobin is Expressed by Alveolar Epithelial Cells. J Biol Chem 2006; 281: 5668-76. DOI: 10.1074/jbc. M509314200
38. Stripp BR, Reynolds SD. Maintenance and Repair of the Bronchiolar Epithelium. Proc Am Thorac Soc 2008; 5: 328-33. DOI: 10.1513/pats.200711-167DR
39. Fehrenbach H, Fehrenbach A, Pan T, et al. Keratinocyte is Growth Factor-Induced Proliferation of Rat Airway Epithelium Restricted to Clara Cells In Vivo. Eur Respir J 2001; 20: 1185-97. DOI: 10.1183/09031936.02.00022702
40. Fernandez-Valdivia R, Zhang Y, Pai S, et al: l7Rn6 Encodes A Novel Protein Required for Clara Cell Function in Mouse Lung Development. Genetics 2006; 172: 389-99. DOI: 10.1534/genetics.105.048736
41. Andersson O, Cassel TN, Sköld CM, et al. Clara Cell Secretory Protein. Chest 2000; 118: 180-2. DOI: 10.1378/chest.118.1.180
42. Adair-Kirk TL, Atkinson JJ, Griffin GL, et al. Distal Airways in Mice Exposed to Cigarette Smoke. Am J Resp Cell Mol Biol 2008; 39: 400-11. 10.1165/rcmb.2007-0295OC DOI:
43. Gupta K, Joshi K, Jindal SK, Rayat CS. Spectrum of Pulmonary Adenocarcinoma with Ultrastructural Correlation: An Autopsy Study from Northern India. Ind J Pathol Microbiol 2008; 51: 3. DOI: 10.4103/0377- 4929.42505
44. Alver G, Çangır AK, Atinkaya C, ve ark. Akciğerin Papiller Adenomu. Ankara Üniversitesi Tıp Fakültesi Mecmuası 2001; 54. 1.
45. Dessy E, Braidotti P, Del Curto B, et al. Peripheral Papillary Tumor of Type II Pneumocytes: A Rare Neoplasm of Undetermined Malignant Potential. Virchovvs Arch 2000; 436(3): 289-95.
46. Mori M, Chiba R, Tezuka F, et al. Papillary Adenoma of Type II Pneumocytes might have Malignant Potential. Virchovvs Arch 1996; 428(3): 195-200.
47. Kuperman DA, Huang X, Nguyenvu L, et al. IL-4 Receptor Signaling in Clara Cells is Required for Allergen- Induced Mucus Production. J İmmunol 2005; 175: 3746- 52.
48. Coppens JT, Van Winkle L, Pinkerton K, Plopper CG. Distribution of Clara Cell Secretory Protein Expression in the Tracheobronchial Airways of Rhesus Monkeys. Am J Physiol Lung Cell Mol Physiol 2007; 292: 1155-62. DOI:10.1152/ajplung.00454.2006
49. Bu derlemeye atıf yapmak için: Elbe H,
50. Eşrefoğlu M. Clara Hücresi. JIUMF 2012; 19(3):
51. 8. DOI: 10.7247/jiumf.19.3.13