Lung chitinolytic activity and chitotriosidase are elevated in chronic obstructive pulmonary disease and contribute to lung inflammation.
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 ChTRase-positive 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)-1beta, IL-8, tumor-necrosis factor (TNF)-alpha, and its type II soluble receptor. Tumor necrosis factor-alpha 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.
Létuvé
Séverine
S
Institut National de la Sante et de la RechercheMedicale (Inserm) U700, 75018 Paris, France.
Kozhich
Alexander
A
Humbles
Alison
A
Brewah
Yambasu
Y
Dombret
Marie-Christine
MC
Grandsaigne
Martine
M
Adle
Homa
H
Kolbeck
Roland
R
Aubier
Michel
M
Coyle
Anthony J
AJ
Pretolani
Marina
M
D000818:Animals; D001249:Asthma / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002478:Cells, Cultured; D002688:Chitinases / Q000378:metabolism* / Q000502:physiology; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D005260:Female; D006596:Hexosaminidases / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008168:Lung / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000209:etiology* / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D018121:Receptors, Cytokine / Q000032:analysis / Q000378:metabolism; D012907:Smoking / Q000378:metabolism; D054928:Validation Studies as Topic
D016207:Cytokines; D018121:Receptors, Cytokine; D006596:Hexosaminidases; C086400:chitotriosidase; D002688:Chitinases