期刊论文详细信息
Clinical and Molecular Allergy
Clara cell protein in nasal lavage fluid and nasal nitric oxide - biomarkers with anti-inflammatory properties in allergic rhinitis
Bijar Ghafouri4  Magnus P Borres1  Jörgen P Palm3  Kristina Irander2 
[1] Phadia AB, Uppsala, Sweden;Allergy Center, University Hospital, Linköping, Sweden;Department of Physiology and Pharmacology, Karolinska Institutet, Sweden;Occupational and Environmental Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, and Centre of Occupational and Environmental Medicine, County Council of Östergötland, Linköping, Sweden
关键词: upper airways;    nasal lavage fluid;    eosinophils;    basophils;    mast cells;    metachromatic cells;    anti-inflammatory effects;    allergic rhinitis;    nasal nitric oxide;    CC16;   
Others  :  790602
DOI  :  10.1186/1476-7961-10-4
 received in 2011-10-21, accepted in 2012-02-06,  发布年份 2012
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【 摘 要 】

Background

Clara cell protein (CC16) is ascribed a protective and anti-inflammatory role in airway inflammation. Lower levels have been observed in asthmatic subjects as well as in subjects with intermittent allergic rhinitis than in healthy controls. Nasal nitric oxide (nNO) is present in high concentrations in the upper airways, and considered a biomarker with beneficial effects, due to inhibition of bacteria and viruses along with stimulation of ciliary motility. The aim of this study was to evaluate the presumed anti-inflammatory effects of nasal CC16 and nNO in subjects with allergic rhinitis.

Methods

The levels of CC16 in nasal lavage fluids, achieved from subjects with persistent allergic rhinitis (n = 13), intermittent allergic rhinitis in an allergen free interval (n = 5) and healthy controls (n = 7), were analyzed by Western blot. The levels of nNO were measured by the subtraction method using NIOX®. The occurrences of effector cells in allergic inflammation, i.e. metachromatic cells (MC, mast cells and basophiles) and eosinophils (Eos) were analyzed by light microscopy in samples achieved by nasal brushing.

Results

The levels of CC16 correlated with nNO levels (r2 = 0.37; p = 0.02) in allergic subjects.

The levels of both biomarkers showed inverse relationships with MC occurrence, as higher levels of CC16 (p = 0.03) and nNO (p = 0.05) were found in allergic subjects with no demonstrable MC compared to the levels in subjects with demonstrable MC. Similar relationships, but not reaching significance, were observed between the CC16 and nNO levels and Eos occurrence. The levels of CC16 and nNO did not differ between the allergic and the control groups.

Conclusions

The correlation between nasal CC16 and nNO levels in patients with allergic rhinitis, along with an inverse relationship between their levels and the occurrences of MC in allergic inflammation, may indicate that both biomarkers have anti-inflammatory effects by suppression of cell recruitment. The mechanisms behind these observations warrant further analyses.

【 授权许可】

   
2012 Irander et al; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Bernard A, Lauwerys R: Low-molecular-weight proteins as markers of organ toxicity with special reference to Clara cell protein. Toxicol Lett 1995, 77:145-151.
  • [2]Broeckaert F, Bernard A: Clara cell secretory protein (CC16): characteristics and perspectives as lung peripheral biomarker. Clin Exp Allergy 2000, 30:469-475.
  • [3]Lakind JS, Holgate ST, Ownby DR, Mansur AH, Helms PJ, Pyatt D, Hays SM: A critical review of the use of Clara cell secretory protein (CC16) as a biomaker of acute or chronic pulmonary effects. Biomarkers 2007, 12:445-467.
  • [4]Lindahl M, Svartz J, Tagesson C: Demonstration of different forms of the anti-inflammatory proteins lipocortin-1 and Clara cell protein-16 in human nasal and bronchoalveolar lavage fluids. Electrophoresis 1999, 20:881-890.
  • [5]Lindahl M, Irander K, Tagesson C, Ståhlbom B: Nasal lavage fluid and proteomics as means to identify the effects of the irritating epoxy chemical dimethylbenzylamine. Biomarkers 2004, 9:56-70.
  • [6]Gomes EC, Stone V, Florida-James G: Impact of heat and pollution on oxidative stress and CC16 secretion after 8 km run. Eur J Appl Physiol 2011, 111:2089-2097.
  • [7]Johansson S, Keen C, Ståhl A, Wennergren G, Benson M: Low levels of CC16 in nasal fluid of children with birch pollen-induced rhinitis. Allergy 2005, 60:638-642.
  • [8]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 2005, 35:473-478.
  • [9]Benson M, Fransson M, Martinsson T, Naluai ÅT, 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 2007, 62:178-183.
  • [10]Lundberg JO: Nitric oxide and the paranasal sinuses. Anat Rec 2008, 291:1479-1484.
  • [11]Borres MP, Irander K, Björkstén B: Nasal metachromatic cells in infants in relation to allergic disease and family history of atopy. Pediatr Allergy Immunol 1991, 4:184-189.
  • [12]Borres MP, Irander K, Björkstén B: Nasal metachromatic cells in infancy in relation to the appearance of atopic disease during the first 6 years of life. Allergy 1997, 52:770-774.
  • [13]Irander K, Borres MP: An 18-year follow-up of allergy development related to nasal metachromatic cell findings during infancy. Allergol Int 2010, 59:193-200.
  • [14]Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976, 72:248-254.
  • [15]American Thoracic Society, European Respiratory Society: ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med 2005, 171:912-930.
  • [16]Palm JP, Graf P, Lundberg JON, Alving K: Characterization of exhaled nitric oxide: introducing a new reproducible method for nasal nitric oxide measurements. Eur Respir J 2000, 16:236-241.
  • [17]Zetterquist W, Pedroletti C, Lundberg JON, Alving K: Salivary contribution to exhaled nitric oxide. Eur Resp J 1999, 13:327-333.
  • [18]Shijubo N, Itoh Y, Yamaguchi T, Imada A, Hirasawa M, Yamada T, Kawai T, Abe S: Clara cell protein-positive epithelial cells are reduced in small airways of asthmatics. Am J Respir Crit Care Med 1999, 160:930-933.
  • [19]de Burbure C, Pignatti P, Corradi M, Malerba M, Clippe A, Dumont X, Moscato G, Mutti A, Bernard A: Uteroglobin-related protein 1 and Clara cell protein in induced sputum of patients with asthma and rhinitis. Chest 2007, 131:172-179.
  • [20]Turner S: The role of exhaled nitric oxide in the diagnosis, management and treatment of asthma. Mini Rev Med Chem 2007, 7:539-542.
  • [21]Barnes PJ, Dweik RA, Gelb AF, Gibson PG, George SC, Grasemann H, Pavord ID, Ratjen F, Silkoff PE, Taylor DR, Zamel N: Exhaled nitric oxide in pulmonary diseases: a comprehensive review. Chest 2010, 138:682-692.
  • [22]Porsbjerg C, Lund TK, Pedersen L, Backer V: Inflammatory subtypes in asthma are related to airway hyperresponsiveness to mannitol and exhaled NO. J Asthma 2009, 46:606-612.
  • [23]Maniscalco M, Sofia M, Pelaia G: Nitric oxide in upper airways inflammatory diseases. Inflamm Res 2007, 56:58-69.
  • [24]Larsson AK, Bäck M, Hjoberg J, Dahlén SE: Inhibition of nitric-oxide synthase enhances antigen-induced contractions and increases release of cysteinyl-leucotrienes in guinea pig lung parenchyma: nitric oxide as a protective factor. J Pharmacol Exp Ther 2005, 315:458-465.
  • [25]Larsson AK, Bäck M, Lundberg JO, Dahlén SE: Specific mediator inhibition by the NO donors SNP and NCX 2057 in the peripheral lung: implications for allergen-induced bronchoconstriction. Respir Res 2009, 10:46. BioMed Central Full Text
  • [26]Coleman JW: Nitric oxide: a regulator of mast cell activation and mast cell-mediated inflammation. Clin Exp Immunol 2002, 129:4-10.
  • [27]Lundberg JO: Airborne nitric oxide: inflammatory marker and aerocrine messenger in man. Acta Physiol Scand Suppl 1996, 633:1-27.
  • [28]Maniscalco M, Sofia M, Carratù L, Higenbottam T: Effect of nitric oxide inhibition on nasal airway resistance after nasal allergen challenge in allergic rhinitis. Eur J Clin Invest 2001, 31:462-466.
  • [29]Moody A, Fergusson W, Wells A, Bartley J, Kolbe J: Nasal levels of nitric oxide as an outcome variable in allergic upper respiratory tract disease: Influence of atopy and hayfever on nNO. Am J Rhinol 2006, 20:425-429.
  • [30]Palm JP, Alving K, Lundberg JO: Characterization of airway nitric oxide in allergic rhinitis: the effect of intranasal administration of L-NAME. Allergy 2003, 58:885-892.
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