YKL-40 is elevated in patients with chronic obstructive pulmonary disease and activates alveolar macrophages.
YKL-40 is a chitin-binding protein that is elevated in patients with various inflammatory conditions associated with ongoing remodeling. We investigated whether the levels of YKL-40 were up-regulated in the circulation and the airways of patients with chronic obstructive pulmonary disease (COPD), and whether it promoted the production of inflammatory mediators from macrophages. Serum, bronchoalveolar lavage (BAL), bronchial biopsies, lung tissue specimens, and alveolar macrophages from never-smokers (n = 15), smokers without COPD (n = 20), and smokers with COPD (n = 30) were assessed for YKL-40 levels and immunolocalization. In addition, YKL-40-induced mediator release from alveolar macrophages was examined. We found that smokers with COPD had elevated levels of YKL-40 in serum (p </= 0.027) and BAL (p </= 0.007), more YKL-40-positive cells in bronchial biopsies (p </= 0.03), and a greater proportion of alveolar macrophages expressing YKL-40 than smokers without COPD or never-smokers. YKL-40 levels in serum and BAL were associated with airflow obstruction (pre-beta(2) agonist forced expiratory volume in 1 s, r(s) = -0.3892, p = 0.0072 and r(s) = -0.5491, p < 0.0001, respectively) and impaired diffusion lung capacity (transfer factor of the lung for carbon monoxide, r(s) = -0.4667, p = 0.002 and r(s) = -0.3854, p = 0.0045, respectively). TNF-alpha stimulated YKL-40 synthesis in alveolar macrophages from smokers with COPD, and exposure of these cells to YKL-40 promoted the release of IL-8, MCP-1, MIP-1alpha, and metalloproteinase-9. We conclude that YKL-40 is up-regulated in COPD, in which it may contribute to tissue inflammation and remodeling by sustaining the synthesis of proinflammatory and fibrogenic chemokines and of metalloproteinases by alveolar macrophages.
Létuvé
Séverine
S
Institut National de la Santé et de la Recherche Médicale Unité 700, Physiopathology and Epidemiology of Respiratory Insufficiency, Paris, France.
Kozhich
Alexander
A
Arouche
Nassim
N
Grandsaigne
Martine
M
Reed
Jennifer
J
Dombret
Marie-Christine
MC
Kiener
Peter A
PA
Aubier
Michel
M
Coyle
Anthony J
AJ
Pretolani
Marina
M
D054392:Adipokines; D000368:Aged; D001980:Bronchi / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D002460:Cell Line; D000071451:Chitinase-3-Like Protein 1; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis* / Q000097:blood / Q000502:physiology; D006801:Humans; D037102:Lectins; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008262:Macrophage Activation / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D012720:Severity of Illness Index
D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins