Abstract
Rationale: We have previously shown that neutrophils from Chronic Obstructive Pulmonary Disease (COPD) patients migrate with reduced accuracy (Sapey et al. AJRCCM 2011; 183:1176-86). There is some evidence to suggest chemokine receptors may be differentially in COPD neutrophils. We sought to determine if differences in receptor function may explain the aberrant neutrophilic migration in COPD.
Methods: Surface expression of CXCR1, CXCR2 and the fMLP receptor (FPR1) was semi quantified by Fluorescence Activated Cell Sorting (FACS) before and at points throughout a 2 hour stimulation time-course with IL-8 or fMLP. CXCR1 and CXCR2 shedding was quantified by ELISA and localisation was assessed by fluorescence microscopy on adhered and fixed neutrophils following stimulation with fMLP.
Results: CXCR1 was significantly lower in quiescent COPD neutrophils compared to health. This difference was rapidly abolished following stimulation with IL-8. No differences were observed in CXCR2 or FPR1 expression. CXCR1 shedding was negligible but there was more CXCR2 shedding detected, although there was no difference between COPD and health. Both COPD and healthy neutrophils appeared to mobilise CXCR1 and CXCR2 to the leading edge once they had been stimulated.
Conclusions: Our novel data on receptor function in stimulated neutrophils suggest that chemokine receptors are unlikely to be an influential factor in the aberrant migration of COPD neutrophils.
- © 2014 ERS