Published ahead of print on November 16, 2006, doi:10.1164/rccm.200507-1152OC Am. J. Respir. Crit. Care Med., Volume 175, Number 5, March 2007, 473-479 A more recent version of this article appeared on March 1, 2007
Submitted on July 26, 2005 Impaired Neutrophil Chemotaxis in Chronic Obstructive Pulmonary Disease (COPD)Takahiro Yoshikawa1,1 Department of Respiratory Cell and Molecular Biology, Division of Infection, Inflammation and Repair, University of Southampton School of Medicine, Southampton, Hampshire, United Kingdom; Department of Respiratory Medicine, Osaka City University, Graduate School of Medicine, Osaka, Japan, 2 Department of Respiratory Cell and Molecular Biology, Division of Infection, Inflammation and Repair, University of Southampton School of Medicine, Southampton, Hampshire, United Kingdom; Department of Human Disease and Genomics, Keele University, Institute of Science and Technology in Medicine, Keele, Staffordshire, United Kingdom, 3 Department of Respiratory Cell and Molecular Biology, Division of Infection, Inflammation and Repair, University of Southampton School of Medicine, Southampton, Hampshire, United Kingdom, 4 Department of Respiratory Medicine, Osaka City University, Graduate School of Medicine, Osaka, Japan * To whom correspondence should be addressed. E-mail: r.djukanovic{at}soton.ac.uk.
Rationale Neutrophilic airway inflammation is considered a major factor in the pathogenesis of chronic obstructive pulmonary disease (COPD), with sputum and bronchoalveolar lavage neutrophil counts broadly correlating with disease severity. The mechanisms responsible for neutrophil accumulation are poorly understood, but they could involve increased influx and/or survival of these cells. Objectives To investigate whether neutrophil chemotactic responsiveness and/or chemotactic activity in airway secretions are increased in subjects with COPD. Methods Chemotaxis experiments were performed using induced sputum supernatants from subjects with and without COPD as a source of chemotactic activity, and neutrophils from healthy donors as responder cells. In addition, chemotactic responses to N-formyl-Met-Leu-Phe (fMLP) and interleukin-8 (IL-8/CXCL8) were studied using neutrophils from healthy subjects and subjects with COPD. Measurements and Main Results As reported in the literature, sputum neutrophil counts were significantly increased in COPD subjects compared to healthy subjects. However, this was associated with reduced chemotactic activity in sputum in COPD, as judged by reduced chemotaxis to the fluid phase of sputum from subjects with COPD compared with healthy subjects. Furthermore, while neutrophils from subjects with stage I COPD had normal responses to fMLP and IL-8, subjects with more severe stage II-IV COPD showed reduced levels of spontaneous migration and chemotaxis to fMLP and IL-8. Conclusions Neither increased chemotactic activity in the airways nor increased chemotactic responsiveness of neutrophils explains the increased number of these cells in subjects with stable COPD. The implications of the observed reduction in neutrophil chemotactic activity remain to be established. Key words: leukocyte chemotaxis, smoking, sputum, neutrophils
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