Impaired monocyte chemotaxis in COPD

Background: COPD is associated with airway neutrophilia. Murine studies have suggested that monocytes serve to attenuate neutrophil accumulation by phagocytosing apoptotic neutrophils. Elevated concentrations of monocytic chemokines have been observed in COPD sputum. Monocytes isolated from individuals suffering with chronic inflammatory disease have demonstrated enhanced adhesion molecule expression suggesting augmented chemotaxis potential. We postulated that monocytes of COPD patients would demonstrate enhanced chemotaxis to sputum supernatant. Methods: PBS (phosphate buffered saline) processed sputum supernatant was obtained from n = 3 COPD and pooled together. CD14+ monocytes were isolated from the peripheral blood of 6 COPD and 8 healthy non-smokers (HNS) by magnetic bead isolation. Monocyte chemotaxis was assayed by transwell diffusion (incorporating a fluorescent DNA probe detection method). All conditions were assayed in triplicate; all triplicate values were utilised in the statistical analysis. Results: COPD sputum supernatant induced CD14+ monocyte chemotaxis. This response was diminished in those CD14+ monocytes isolated from COPD compared to HNS (see table). CD14+ monocytes isolated from older (>50 years) HNS demonstrated enhanced chemotaxis compared to those from HNS <50 years (16% vs 8.8%; p<0.0001). Conclusion COPD CD14+ monocytes demonstrate functional impairment as evidenced by diminished migratory capabilities. Attenuated monocyte chemotaxis may contribute to neutrophil accumulation in the airways of COPD patients.