YKL-40 Is Elevated in Patients with Chronic Obstructive Pulmonary Disease and Activates Alveolar Macrophages

Journal of Immunology - Tập 181 Số 7 - Trang 5167-5173 - 2008
S. Létuvé1,2, Alexander Kozhich3, Nassim Arouche1,2, Martine Grandsaigne1,2, Jennifer L. Reed3, Marie-Christine Dombret4,5, Peter A. Kiener3, Michel Aubier1,4,5,2, Anthony J. Coyle3, Marina Pretolani1,5,2
1*Institut National de la Santé et de la Recherche Médicale Unité 700, Physiopathology and Epidemiology of Respiratory Insufficiency, Paris, France;
2†Université Paris 7, Faculté de Médecine Denis Diderot, Site Bichat, Paris, France;
3‡Department of Autoimmunity, Inflammation and Respiratory Disease, MedImmune, Gaithersburg, MD 20878;
4§Département de Pneumologie A, Centre Hospitalier Universitaire Bichat-Claude Bernard, Paris, France; and
5¶Assistance Publique Hôpitaux de Paris, Paris, France

Tóm tắt

Abstract 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-β2 agonist forced expiratory volume in 1 s, rs = −0.3892, p = 0.0072 and rs = −0.5491, p < 0.0001, respectively) and impaired diffusion lung capacity (transfer factor of the lung for carbon monoxide, rs = −0.4667, p = 0.002 and rs = −0.3854, p = 0.0045, respectively). TNF-α 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-1α, 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.

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Journal of Immunology

Tập 181 Số 7

5167-5173

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