Impaired Neutrophil Chemotaxis in Chronic Obstructive Pulmonary Disease

• Published in: American Journal of Respiratory and Critical Care Medicine Vol. 175; no. 5; pp. 473 - 479
• Main Authors: Yoshikawa, Takahiro, Dent, Gordon, Ward, Jon, Angco, Gilbert, Nong, Guangmin, Nomura, Naho, Hirata, Kazuto, Djukanovic, Ratko
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 01.03.2007; American Thoracic Society; American Lung Association
• Subjects: Airway management; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Bronchitis; Bronchoalveolar Lavage Fluid; Bronchoalveolar Lavage Fluid - cytology; Chemotaxis, Leukocyte; Chemotaxis, Leukocyte - drug effects; Chemotaxis, Leukocyte - physiology; Chronic obstructive pulmonary disease; Chronic obstructive pulmonary disease, asthma; Cytokines; Female; Humans; Intensive care medicine; Interleukin-8; Lavage; Leukocyte Count; Male; Medical sciences; Middle Aged; N-Formylmethionine Leucyl-Phenylalanine; N-Formylmethionine Leucyl-Phenylalanine - analogs & derivatives; Neutrophils; Pneumology; Pulmonary Disease, Chronic Obstructive; Pulmonary Disease, Chronic Obstructive - pathology; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Severity of Illness Index; Sputum; Sputum - cytology; Tumor necrosis factor-TNF; United Kingdom > UK; Lung disease; Intensive care; Respiratory disease; Chronic disease; Sputum; Bronchus disease; Obstructive pulmonary disease; Neutrophil; Chemotaxis; neutrophils; Resuscitation; chronic obstructive pulmonary disease
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200507-1152OC

Neutrophilic airway inflammation is considered to be 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. To investigate whether neutrophil chemotactic responsiveness and/or chemotactic activity in airway secretions are increased in subjects with COPD. 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. As reported in the literature, sputum neutrophil counts were significantly increased in subjects with COPD compared with 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, whereas 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. 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.