Overexpression of chitotriosidase and YKL-40 in peripheral blood and sputum of healthy smokers and patients with chronic obstructive pulmonary disease

Abstract

Background

Despite the absence of endogenous chitin in humans, chitinases are present in the serum of healthy subjects and their levels are increased in a variety of chronic inflammatory conditions. It has been shown that chitotriosidase and structurally related chitinase-like protein-YKL-40 contribute to the pathogenesis of COPD. However, details regarding the relation of their systemic and local airways levels remain unknown.

Objectives

To examine peripheral blood and sputum chitotriosidase and YKL-40 expression in smokers and patients with COPD.

Methods

Forty patients with COPD, 20 healthy smokers and 10 healthy never-smokers were studied. Serum and induced sputum chitotriosidase protein and activity levels, YKL-40 concentrations, and their gene expression in sputum cells and peripheral blood mononuclear cells (PBMC) were evaluated.

Results

Both chitotriosidase protein levels and activity were higher in sputum obtained from COPD subjects compared to healthy never-smokers (P<0.05 and P<0.01, respectively). A similar pattern was observed for PBMC chitotriosidase mRNA expression (P<0.001). YKL-40 serum concentrations were elevated in healthy smokers and COPD subjects compared to healthy never-smokers (P<0.001 and P<0.01, respectively). In sputum, YKL-40 levels were increased in COPD compared to healthy never-smokers (P<0.01). PBMC YKL-40 mRNA expression was increased in COPD and healthy smokers compared to healthy never-smokers (P<0.0001). No associations were found between chitotriosidase or YKL-40 peripheral blood levels and sputum levels.

Conclusions

Our results demonstrate that chitotriosidase and YKL-40 are overexpressed in peripheral blood and airways in both healthy smokers and COPD subjects which may indicate smoking-related activation of macrophages, neutrophils, and epithelial cells.

Keywords:

• chitotriosidase
• CHIT1
• YKL-40
• chitinase
• chitin-like protein
• COPD

Acknowledgments

This work was funded by Medical University of Lodz. The costs of this study were defrayed from regular finances of the Department of Pneumology and Allergy 503/1-151-03/503-11-002-18. The abstract version of this paper was presented at the 28th ERS International Congress in Paris as a poster presentation with interim findings and the poster’s abstract has been published.⁷⁸

Author contributions

Study conception – SM and PG; design – SM, DT, EBL, AA, WJP, PG; acquisition of data – SM, DT, KS, JK, ZK, HJ. All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.