Lung Chitinolytic Activity and Chitotriosidase Are Elevated in Chronic Obstructive Pulmonary Disease and Contribute to Lung Inflammation

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation and emphysematous alveolar destruction. In this study, we have investigated whether chitotriosidase (ChTRase) and acidic mammalian chitinase, two chitinases with chitinolytic activity, are selectively augmented in COPD and contribute to its pathogenesis. We found that smokers with COPD, but not asthmatics, had higher chitinolytic activity and increased levels of ChTRase in bronchoalveolar lavage, more ChTRasepositive cells in bronchial biopsies, and an elevated proportion of alveolar macrophages expressing ChTRase than smokers without COPD or never-smokers. ChTRase accounted for approximately 80% of bronchoalveolar lavage chitinolytic activity, while acidic mammalian chitinase was undetectable. Bronchoalveolar lavage chitinolytic activity and ChTRase were associated with airflow obstruction and emphysema and with the levels of interleukin (IL)؊1␤, IL-8, tumor-necrosis factor (TNF)-␣, and its type II soluble receptor. Tumor necrosis factor-␣ stimulated ChTRase release only from alveolar macrophages from smokers with COPD, and exposure of these cells to ChTRase promoted the release of IL-8, monocyte-chemoattractant protein-1, and metalloproteinase-9. Finally, ChTRase overexpression in the lung of normal mice promoted macrophage recruitment and the synthesis of the murine homologue of IL-8, keratinocyte-derived cytokine, and of monocyte-chemoattractant protein-1. We conclude that pulmonary ChTRase overexpression may represent a novel important mechanism involved in COPD onset and progression. (Am J

Chitinase 1 Is a Biomarker for and Therapeutic Target in Scleroderma-Associated Interstitial Lung Disease That Augments TGF-β1 Signaling

“…These studies revealed very few Chit1-expressing cells in control lungs, as well as significantly increased numbers in lungs from patients with end-stage SSc-ILD (2.0 ± 0.37 versus 18.5 ±2.35, p <0.0001; Fig 1B). Consistent with a previous report (37), in the normal lung Chit1 expression was restricted to a low-level signal in macrophages with essentially no staining in epithelial cells (Fig. 1C).…”

“…Because Chit1 is known to be induced by exposure to cigarette smoke, we performed an initial set of exploratory analyses in control patients with and without a history of smoking. In this study, we found that, as was previously reported (37), circulating Chit1 activity was significantly higher in the plasma of smokers even in the absence of any known lung disease (data not shown). Because we were interested in whether Chit1 reflects pulmonary fibrosis, and not how cigarette smoke confounds these results, patients with a known history of active or prior cigarette smoke exposure were excluded from this study.…”

Increased YKL-40 and Chitotriosidase in Asthma and Chronic Obstructive Pulmonary Disease

“…Increased BAL chitotriosidase activity has been found in smokers (4,5), and elevated circulating YKL-40 has been found in patients with COPD compared with control subjects, in whom levels may relate to smoking history (37,38). In the present study, no differences were observed between current smokers and ex-smokers, suggesting that current smoke exposure per se is not responsible for increased chitinase levels.…”

“…In recent years, these proteins have been linked to airway inflammation (2). Although AMCase has been associated with airway inflammation predominantly in animal models (3), chitotriosidase activity is increased in the airways of smokers and subjects with chronic obstructive pulmonary disease (COPD) compared with healthy control subjects (4,5), as well as in the serum of patients with asthma (6). YKL-40 levels are increased in the serum and lungs of patients with asthma compared with healthy control subjects, and they correlate with markers of disease severity (7,8).…”

Smoking, inflammation and small cell lung cancer: recent developments

“…Lung macrophages are found in abundance in COPD and display a mixed phenotype of polarization markers, such as inducible nitric oxide synthase (iNOS)/matrix metalloproteinase 9 (MMP9) for M1 and CD163 scavenger receptor/MMP12 for M2, respectively, indicating dysregulated macrophage function. The mediators that induce expression of M2 markers in COPD-associated macrophages have not been comprehensively characterized [32]. Most of the inflammatory proteins in COPD in 5-year survival rates of at least 20 % [57,58].…”