Clara Cell Protein Human ELISA

Summary

Human Clara Cell Protein (CC16, CC10 and also called uteroglobin, urinary protein 1 or Clara Cell Secretory Protein) belongs to the family of secretoglobins and is a secreted protein product of non-ciliated bronchiolar Clara cells. Its function remains to be elucidated but there is convincing data suggesting its phospholipase A2 inhibitory activity as well as a number of other immunomodulatory features including inhibition of interferon gamma signaling and Th1 vs. Th2 lymphocyte regulation. It was proposed as a potential peripheral marker of respiratory epithelial injury and bronchial dysfunction. In serum, its increase is associated with age, asbestos, nitrogen chloride and ozone exposure, sarcoidosis and high PEEP ventilation. Decreased serum CC16 levels are found after pulmonary resection, in silica-exposed workers, smokers and in asthma. Decreased CC16 concentrations were also found in the amniotic fluid of fetuses suffering from pulmonary hypoplasia caused by various mechanisms (diaphragmatic hernia, diabetic fetopathy, Turner and Down syndrome).

Features

• European Union: for in vitro diagnostic use
• Rest of the world: for research use only!
• The total assay time is less than 4 hours
• The kit measures total (homodimeric) Clara cell protein in serum and plasma (EDTA,

citrate, heparin)

• Assay format is 96 wells
• Quality Controls are human serum based
• Standard is purified native protein based
• Components of the kit are provided ready to use, concentrated or lyophilized

Research topic

Immune Response, Infection and Inflammation

Assay format

Sandwich ELISA, Biotin-labelled antibody

Applications

Plasma-Citrate, Plasma-EDTA, Plasma-Heparin, Serum

Sample requirements

5 µl/well

Storage/Shipping

Store the kit at 2–8°C. Under these conditions, the kit is stable until the expiration date (see label on the box).

Calibration Curve

Calibration range

2 to 100 ng/ml

Limit of detection

20 pg/ml

Intra-assay (Within-Run, n=8)

CV = 7.0 %

Inter-assay (Run-to-Run, n=4)

CV = 6.0 %

Spiking Recovery

106.4 %

Dilution Linearity

101.2 %

Cross-Reactivity

References to this product

• Alexis NE, Lay JC, Haczku A, Gong H, Linn W, Hazucha MJ, Harris B, Tal-Singer R, Peden DB. Fluticasone propionate protects against ozone-induced airway inflammation and modified immune cell activation markers in healthy volunteers. Environ Health Perspect. 2008 Jun;116 (6):799-805
• Andersson L, Lundberg PA, Barregard L. Methodological aspects on measurement of Clara cell protein in urine as a biomarker for airway toxicity, compared with serum levels. J Appl Toxicol . Dec 22;27(1):60-66 (2006)
• Benson M, Fransson M, Martinsson T, Naluai AT, Uddman R, Cardell LO. Inverse relation between nasal fluid Clara Cell Protein 16 levels and symptoms and signs of rhinitis in allergen-challenged patients with intermittent allergic rhinitis. Allergy . Feb;62(2):178-83 (2007)
• Benson M, Jansson L, Adner M, Luts A, Uddman R, Cardell LO. Gene profiling reveals decreased expression of uteroglobin and other anti-inflammatory genes in nasal fluid cells from patients with intermittent allergic rhinitis. Clin Exp Allergy . Apr;35(4):473-8 (2005)
• Bourdin A, Kotsimbos T, Nguyen K, Vachier I, Mainprice B, Farce M, Paganin F, Marty-Ane C, Vernhet H, Godard P, Chanez P. Non-invasive assessment of small airway remodelling in smokers. COPD. 2010 Apr;7 (2):102-10
• Bourdin A, Kotsimbos T, Nguyen K, Vachier I, Mainprice B, Farce M, Paganin F, Marty-Ane C, Vernhet H, Godard P, Chanez P. Non-invasive assessment of small airway remodelling in smokers. COPD. 2010 Apr;7 (2):102-10
• Chimenti L, Morici G, Paterno A, Bonanno A, Vultaggio M, Bellia V, Bonsignore MR. Environmental conditions, air pollutants, and airway cells in runners: a longitudinal field study. J Sports Sci. 2009 Jul;27 (9):925-35
• Coppens JT, Van Winkle LS, Pinkerton K, Plopper CG. Distribution of Clara cell secretory protein expression in the tracheobronchial airways of rhesus monkeys. Am J Physiol Lung Cell Mol Phy. 2007 May;292 (5):L1155-62
• Diamond JM, Kawut SM, Lederer DJ, Ahya VN, Kohl B, Sonett J, Palmer SM, Crespo M, Wille K, Lama VN, Shah PD, Orens J, Bhorade S, Weinacker A, Demissie E, Bellamy S, Christie JD, Ware LB. Elevated plasma clara cell secretory protein concentration is associated with high-grade primary graft dysfunction. Am J Transplant. 2011 Mar;11 (3):561-7
• Ellingsen DG, Ulvestad B, Andersson L, Barregard L. Pneumoproteins and inflammatory biomarkers in asphalt pavers. Biomarkers. 2010 Sep;15 (6):498-507
• Fransson M, Adner M, Uddman R, Cardell LO. Lipopolysaccharide-induced down-regulation of uteroglobin in the human nose. Acta Otolaryngol. 2007 Mar;127 (3):285-91
• Gaber F, Daham K, Higashi A, Higashi N, Gulich A, Delin I, James A, Skedinger M, Gyllfors P, Nord M, Dahlen SE, Kumlin M, Dahlen B. Increased levels of cysteinyl-leukotrienes in saliva, induced sputum, urine and blood from patients with aspirin-intolerant asthma. Thorax. 2008 Dec;63 (12):1076-82
• Harvey BG, Heguy A, Leopold PL, Carolan BJ, Ferris B, Crystal RG. Modification of gene expression of the small airway epithelium in response to cigarette smoking. J Mol Med . Jan;85(1):39-53 (2007)
• Kropski JA, Fremont RD, Calfee CS, Ware LB. Clara cell protein (CC16), a marker of lung epithelial injury, is decreased in plasma and pulmonary edema fluid from patients with acute lung injury. Chest. 2009 Jun;135 (6):1440-7
• Kucejko W, Chyczewska E, Naumnik W, Ossolinska M. Concentration of surfactant protein D, Clara cell protein CC-16 and IL-10 in bronchoalveolar lavage (BAL) in patients with sarcoidosis, hypersensivity pneumonitis and idiopathic pulmonary fibrosis. Folia Histochem Cytobiol. 2009;47 (2):225-30
• Liu Z, Lu X, Zhang XH, Bochner BS, Long XB, Zhang F, Wang H, Cui YH. Clara cell 10-kDa protein expression in chronic rhinosinusitis and its cytokine-driven regulation in sinonasal mucosa. Allergy. 2009 Jan;64 (1):149-57
• Lomas DA, Silverman EK, Edwards LD, Miller BE, Coxson HO, Tal-Singer R. Evaluation of serum CC-16 as a biomarker for COPD in the ECLIPSE cohort. Thorax. 2008 Dec;63 (12):1058-63
• Madsen C, Durand KL, Nafstad P, Schwarze PE, Ronningen KS, Haheim LL. Associations between environmental exposures and serum concentrations of Clara cell protein among elderly men in Oslo, Norway. Environ Res. 2008 Nov;108 (3):354-60
• Martin AC, Laing IA, Khoo SK, Zhang G, Rueter K, Teoh L, Taheri S, Hayden CM, Geelhoed GC, Goldblatt J, LeSouef PN. Acute asthma in children: Relationships among CD14 and CC16 genotypes, plasma levels, and severity. Am J Respir Crit Care Med . Mar 15 173(6):617-22 (2006)
• Mattsson J, Remberger M, Andersson O, Sundberg B, Nord M. Decreased serum levels of clara cell secretory protein (CC16) are associated with bronchiolitis obliterans and may permit early diagnosis in patients after allogeneic stem-cell transplantation. Transplantation. 2005 May 27;79 (10):1411-6
• Nor J. Exposure, lung function and inflammation markers in asphalt workers. Epidemiol. 2009; 19 (2);:229-234
• Romberg K, Bjermer L, Tufvesson E. Exercise but not mannitol provocation increases urinary Clara cell protein (CC16) in elite swimmers. Respir Med. 2010 Aug 7;
• Sarafidis K, Stathopoulou T, Diamanti E, Soubasi V, Agakidis C, Balaska A, Drossou V. Clara cell secretory protein (CC16) as a peripheral blood biomarker of lung injury in ventilated preterm neonates. Eur J Pediatr. 2008 Nov;167 (11):1297-303
• Schnapp LM, Donohoe S, Chen J, Sunde DA, Kelly PM, Ruzinski J, Martin T, Goodlett DR. Mining the acute respiratory distress syndrome proteome: identification of the insulin-like growth factor (IGF)/IGF-binding protein-3 pathway in acute lung injury. Am J Pathol . Jul;169(1):86-95 (2006)
• Sims MW, Tal-Singer RM, Kierstein S, Musani AI, Beers MF, Panettieri RA, Haczku A. Chronic obstructive pulmonary disease and inhaled steroids alter surfactant protein D (SP-D) levels: a cross-sectional study. Respir Res. 2008;9:13
• Sin DD, Leung R, Gan WQ, Man SP. Circulating surfactant protein D as a potential lung-specific biomarker of health outcomes in COPD: a pilot study. BMC Pulm Med. 2007;7:13
• Thomas W, Kawczynska-Leda N, Seidenspinner S, Chmielnicka-Kopaczyk M, Marx A, Szymankiewicz N, Gadzinowski J, Speer CP. Funiculitis und niedrigere Konzentrationen von Clara-Zell-Sekretorischem Protein (CC10) im Trachealsekret (TS) sehr kleiner Frühgeborener (VLBW) in den ersten Lebenstagen.
• Ulvestad B, Randem BG, Andersson L, Ellingsen DG, Barregard L. Clara cell protein as a biomarker for lung epithelial injury in asphalt workers. J Occup Environ Med. 2007 Oct;49 (10):1073-8
• Vaes B, Pasquet A, Wallemacq P, Rezzoug N, Mekouar H, Olivier PA, Legrand D, Mathei C, Van Pottelbergh G, Degryse J. The BELFRAIL (BFC80+) study: a population-based prospective cohort study of the very elderly in Belgium. BMC Geriatr. 2010;10:39
• Yang KD, Ou CY, Chang JC, Chen RF, Liu CA, Liang HM, Hsu TY, Chen LC, Huang SK. Infant frequent wheezing correlated to Clara cell protein 10 (CC10) polymorphism and concentration, but not allergy sensitization, in a perinatal cohort study. J Allergy Clin Immunol. 2007 Oct;120 (4):842-8

References to summary

• Backé E, Lotz G, Tittelbach U, Plitzko S, Gierke E and Schneider WD: Immunological biomarkers in salt miners exposed to salt dust, diesel exhaust and nitrogen oxides. Int Arch Occup Environ Health, Jun; 77(5):319–27 (2004)
• Signor L, Tigani B, Beckmann N, Falchetto R and Stoeckli M: Two-dimensional electrophoresis protein profiling and identification in rat bronchoalveolar lavage fluid following allergen and endotoxin challenge. Proteomics, Jul; 4(7):2101–10 (2004)
• Shijubo N., Kawabata I., Sato N., Itoh Y.: Clinical Aspects of Clara Cell 10-kDa Protein/ Uteroglobin (Secretoglobin 1A1), Current Pharmaceutical Design, 9, 1139–1149, (2003)
• Nord M., Schubert K., Cassel T., Andersson O., Riise G.: Decreased serum and bronchoalveolar lavage levels of Clara cell secretory protein (CC16) is associated with bronchiolitis obliterans syndrome and airway neutrophilia in lung transplant recipients. Transplantation, 73, 1264–1269, (2002)
• Petrek M., Hermans C., Kolek V., Fialova J., Bernard A.: Clara cell protein (CC16) in serum and bronchoalveolar lavage fluid of subjects exposed to asbestos. Biomarkers, 7(1), 58–67, (2002)
• Robin M., Dong P., Hermans C., Bernard A., Bersten A.D., Doyle I.R.: Serum levels of CC16, SP-A and SP-B reflect tobacco-smoke exposure in asymptomatic subjects. Eur Respir J, 20(5), 1152–1162, (2002)
• Hermans C., Petrek M., Kolek V., Weynand B., Pieters T., Lambert M., Bernard A.: Serum Clara cell protein (CC16), a marker of the integrity of the air-blood barrier in sarcoidosis. Eur Respir J, 18(3), 507–514 (2001)
• Linnoila I., Szabo E., deMayo F., Witschi H., Sabourin C., Malkinson A.: The role of CC10 in pulmonary carcionogenesis: from a marker to tumor suppression. Annals of the New York Academy of Science, 923, 249–267, (2000)
• Broeckaert F., Clippe A., Knoops B., Hermans C. and Bernard A.: Clara cell secretory protein (CC16): features as a peripheral lung biomarker. Annals of the New York Academy of Science, 923, 68–77, (2000)
• Shijubo N., Itoh Y., Yamaguchi T., Abe S.: Development of an enzyme-linked immunosorbent assay for Clara cell 10-kDa protein: in pursuit of clinical significance of sera in patients with asthma and sarcoidosis. Annals of the New York Academy of Science, 923, 268–279, (2000)
• Bernard A., Roels H., Lauwerys R., Witters R., Gielens C., Soumillion A. et al.: Human urinary protein 1: Evidence for identity with the Clara cell protein and occurrence in respiratory tract and urogenital secretions. Clin Chim Acta, 207, 239–249, (1992) Human Clara Cell Protein ELISA (page 19 of 24) VERSION 04 130707 03
• Bernard A., Lauwerys R., Noel A., Vandeleene B., Lambert A.: Urine protein 1: a sexdependent marker of tubular or glomerular dysfunction. Clin Chem, 35, 2141–2142, (1989)
• Jackson P.J., Turner R., Keen J.N., Brooksbank R.A., Cooper E.H.: Purification and partial amino acid sequence of human urine protein 1. Evidence for homology with rabbit uteroglobin. J Chromatography, 452, 359–367, (1988)

By research topic:

• Immune Response, Infection and Inflammation

By molecule:

• Clara Cell Protein

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