Lipocalin-2: a biomarker potentially associated with predisposition to COPD

Background: Smokers undergo frequent and severe respiratory viral infections. We hypothesize that the latter induce pathways eventually leading to COPD. If so, this would allow to identify smokers at increased risk for COPD and therefore their targeted inclusion in smoking cessation and drug intervention programs. Aim: To identify biomarkers associated with predisposition to COPD and to validate these biomarkers in lung samples from COPD patients. Methods: To model heavy smoking, female C57Bl6/J mice were exposed daily to CS or air for 24days. One hour after the last exposure, mice were treated intranasally with PBS or TLR3-ligand PolyIC for 24hrs. Then, BALF was collected and analyzed by 2D-gel electrophoresis coupled with mass-spectrometry (MS). The results were correlated with BAL transcriptome of COPD patients and with lung transcriptome of an independent COPD mouse model. The set of overlapping markers was then confirmed in lung and serum of GOLD stage-III/IV COPD patients. Results: MS showed 41 differentially-expressed proteins in smoke+PolyIC group. The correlation of these proteins with BAL transcriptome of COPD patients showed 7 regulated molecules. One of these molecules, LCN2, was induced in human COPD lung and mouse BALF. The results were confirmed by qRT-PCR, IF and WB. Conclusion: LCN2 was pre-identified in a mouse CS-model with viral trigger. It is abundant in club and ciliated cells and is increased in the bronchiolar epithelium of COPD patients. As a result, it could be affected by CS and viral-trigger since it is localized directly underneath of the apical surface of airway epithelia. To test if LCN2 qualifies as a biomarker predicting COPD it should be assessed in mild COPD and in sputum samples.