Clara cell protein as a marker of Clara cell damage and bronchoalveolar blood barrier permeability

The 16 kDa Clara cell protein (CC16), an abundant component of airway secretions, has recently been proposed in humans as a pulmonary marker measurable not only in bronchoalveolar lavage fluid (BALF) but also in serum. The aim of the present study was to investigate the changes and determinants of CC16 concentrations in these fluids in normal rats and rats with lung injury. Female Sprague-Dawley rats were given a single i.p. injection of arachis oil (n=20) or chemicals in arachis oil (n=10) that mainly damage Clara cells (4-ipomeanol (IPO) 8 mg x kg(-1) and methylcyclopentadienyl manganese tricarbonyl (MMT) 5 mg x kg(-1)) or endothelial cells (alpha-naphthylthiourea (ANTU) 5 mg x kg(-1)). CC16 concentration (mean+/-sD in microg x L(-1)), measured by a sensitive latex immunoassay, was significantly reduced in BALF of all treated groups (IPO 380+/-100; MMT 730+/-200; ANTU 1,070+/-200; controls 1,700+/-470). The same pattern of decrease was observed in the labelling of Clara cells with an anti-CC16 antiserum as well as in the CC16 messenger ribonucleic acid levels assessed by Northern enzyme-linked immunosorbent assay. In serum, by contrast, CC16 was significantly increased in all treated groups (IPO 31+/-7; MMT 22+/-12; ANTU 52+/-24; controls 15+/-6). This rise of CC16 in serum was associated with an elevation of albumin in BALF which is an index of increased bronchoalveolar/blood barrier permeability. In conclusion, lung injury induces a decrease of the 16 kDa Clara cell protein in bronchoalveolar lavage fluid owing to a reduced production by damaged Clara cells, and an increase in serum protein levels resulting from its enhanced leakage across the bronchoalveolar/blood barrier. This study provides new insights into the understanding of the changes of lung secretory proteins in bronchoalveolar lavage fluid and serum.

This article has been cited by other articles:

				L Barregard, G Sallsten, L Andersson, A-C Almstrand, P Gustafson, M Andersson, and A-C Olin Experimental exposure to wood smoke: effects on airway inflammation and oxidative stress Occup. Environ. Med., May 1, 2008; 65(5): 319 - 324. [Abstract] [Full Text] [PDF]

				S. J. Bolton, K. Pinnion, C. V. Marshall, E. Wilson, J. E. Barker, V. Oreffo, and M. L. Foster Changes in Clara Cell 10 kDa Protein (CC10)-positive Cell Distribution in Acute Lung Injury Following Repeated Lipopolysaccharide Challenge in the Rat Toxicol Pathol, April 1, 2008; 36(3): 440 - 448. [Abstract] [Full Text] [PDF]

				V. Starosta, F. Ratjen, E. Rietschel, K. Paul, and M. Griese Anti-inflammatory cytokines in cystic fibrosis lung disease Eur. Respir. J., September 1, 2006; 28(3): 581 - 587. [Abstract] [Full Text] [PDF]

				W.-J. P. van Boven, W. B. M. Gerritsen, P. Zanen, J. C. Grutters, H. P. A. van Dongen, A. Bernard, and L. P. H. J. Aarts Pneumoproteins as a Lung-Specific Biomarker of Alveolar Permeability in Conventional On-pump Coronary Artery Bypass Graft Surgery vs Mini-Extracorporeal Circuit: A Pilot Study Chest, April 1, 2005; 127(4): 1190 - 1195. [Abstract] [Full Text] [PDF]

				K L Timonen, G Hoek, J Heinrich, A Bernard, B Brunekreef, J de Hartog, K Hameri, A Ibald-Mulli, A Mirme, A Peters, et al. Daily variation in fine and ultrafine particulate air pollution and urinary concentrations of lung Clara cell protein CC16 Occup. Environ. Med., November 1, 2004; 61(11): 908 - 914. [Abstract] [Full Text] [PDF]

				S. Yoshikawa, J. A. King, S. D. Reynolds, B. R. Stripp, and J. C. Parker Time and pressure dependence of transvascular Clara cell protein, albumin, and IgG transport during ventilator-induced lung injury in mice Am J Physiol Lung Cell Mol Physiol, March 1, 2004; 286(3): L604 - L612. [Abstract] [Full Text] [PDF]

				J. C. Parker and M. I. Townsley Evaluation of lung injury in rats and mice Am J Physiol Lung Cell Mol Physiol, February 1, 2004; 286(2): L231 - L246. [Abstract] [Full Text] [PDF]

				O. Lesur, C. Hermans, J.-F. Chalifour, J. Picotte, B. Levy, A. Bernard, and D. Lane Mechanical ventilation-induced pneumoprotein CC-16 vascular transfer in rats: effect of KGF pretreatment Am J Physiol Lung Cell Mol Physiol, February 1, 2003; 284(2): L410 - L419. [Abstract] [Full Text] [PDF]

				E. R. Swenson, M. Maggiorini, S. Mongovin, J. S. R. Gibbs, I. Greve, H. Mairbaurl, and P. Bartsch Pathogenesis of High-Altitude Pulmonary Edema: Inflammation Is Not an Etiologic Factor JAMA, May 1, 2002; 287(17): 2228 - 2235. [Abstract] [Full Text] [PDF]

				T. M. Watson, S. D. Reynolds, G. W. Mango, I.-M. Boe, J. Lund, and B. R. Stripp Altered lung gene expression in CCSP-null mice suggests immunoregulatory roles for Clara cells Am J Physiol Lung Cell Mol Physiol, December 1, 2001; 281(6): L1523 - L1530. [Abstract] [Full Text] [PDF]

				A. NEMMAR, H. VANBILLOEN, M. F. HOYLAERTS, P. H. M. HOET, A. VERBRUGGEN, and B. NEMERY Passage of Intratracheally Instilled Ultrafine Particles from the Lung into the Systemic Circulation in Hamster Am. J. Respir. Crit. Care Med., November 1, 2001; 164(9): 1665 - 1668. [Abstract] [Full Text] [PDF]

				E. BERGAMASCHI, G. DE PALMA, P. MOZZONI, S. VANNI, M. V. VETTORI, F. BROECKAERT, A. BERNARD, and A. MUTTI Polymorphism of Quinone-metabolizing Enzymes and Susceptibility to Ozone-induced Acute Effects Am. J. Respir. Crit. Care Med., May 1, 2001; 163(6): 1426 - 1431. [Abstract] [Full Text]