HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Létuvé, S. Articles by Pretolani, M. Search for Related Content PubMed PubMed Citation Articles by Létuvé, S. Articles by Pretolani, M.

YKL-40 Is Elevated in Patients with Chronic Obstructive Pulmonary Disease and Activates Alveolar Macrophages¹

Séverine Létuvé^2,*,, Alexander Kozhich^2,, Nassim Arouche^*,, Martine Grandsaigne^*,, Jennifer Reed, Marie-Christine Dombret^,¶, Peter A. Kiener, Michel Aubier^*,,,¶, Anthony J. Coyle and Marina Pretolani^3,*,,¶

^* Institut National de la Santé et de la Recherche Médicale Unité 700, Physiopathology and Epidemiology of Respiratory Insufficiency, Paris, France; Université Paris 7, Faculté de Médecine Denis Diderot, Site Bichat, Paris, France; Department of Autoimmunity, Inflammation and Respiratory Disease, MedImmune, Gaithersburg, MD 20878; Département de Pneumologie A, Centre Hospitalier Universitaire Bichat-Claude Bernard, Paris, France; and ^¶ Assistance Publique Hôpitaux de Paris, Paris, France

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, 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- 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-1, 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Fondation pour la Recherche Médicale (fellowship to S.L.) and by grants from the Agence Nationale de la Recherche (Santé et Environnement-Santé Travail) and from MedImmune.

² S.L. and A.K. contributed equally to this study.

³ Address correspondence and reprint requests to Dr. Marina Pretolani, Inserm Unité 700, Faculté de Médecine Denis Diderot, Site Bichat - 16, rue Henri Huchard, 75018 Paris, France. E-mail address: marina.pretolani{at}inserm.fr

⁴ Abbreviations used in this paper: COPD, chronic obstructive pulmonary disease; BAL, bronchoalveolar lavage; DL_CO, transfer factor of the lung for carbon monoxide; GOLD, Global Initiative for Obstructive Lung Disease; MMP, matrix metalloproteinase.

This article has been cited by other articles:

				E. Agapov, J. T. Battaile, R. Tidwell, R. Hachem, G. A. Patterson, R. A. Pierce, J. J. Atkinson, and M. J. Holtzman Macrophage Chitinase 1 Stratifies Chronic Obstructive Lung Disease Am. J. Respir. Cell Mol. Biol., October 1, 2009; 41(4): 379 - 384. [Abstract] [Full Text] [PDF]

				K. M. Henningsen, S. K. Therkelsen, J. S. Johansen, H. Bruunsgaard, and J. H. Svendsen Plasma YKL-40, a new biomarker for atrial fibrillation? Europace, August 1, 2009; 11(8): 1032 - 1036. [Abstract] [Full Text] [PDF]

				Y. Cai, R. K. Kumar, J. Zhou, P. S. Foster, and D. C. Webb Ym1/2 Promotes Th2 Cytokine Expression by Inhibiting 12/15(S)-Lipoxygenase: Identification of a Novel Pathway for Regulating Allergic Inflammation J. Immunol., May 1, 2009; 182(9): 5393 - 5399. [Abstract] [Full Text] [PDF]