A unique protein profile of peripheral neutrophils from COPD patients does not reflect cytokine-induced protein profiles of neutrophils in vitro

Using fluorescence 2-dimensional difference gel electrophoresis we investigated differentially regulated proteins in peripheral neutrophils from COPD patients and healthy age-matched control subjects. Furthermore, protein profiles from COPD patients were compared with those of neutrophils of healthy age-matched controls that were stimulated with TNFα and/or GM-CSF in vitro. Protein gels were compared using DeCyder 7.0 software.We identified 7 significantly regulated protein spots between peripheral neutrophils from COPD patients and age-matched healthy control subjects. Stimulation of peripheral neutrophils with TNFα, GM-CSF or TNFα + GM-CSF in vitro resulted in 13, 20 and 22 regulated protein spots, respectively. However, these cytokine-induced protein differences did not correspond with the protein differences found in neutrophils from COPD patients.These results show that neutrophils from COPD patients have a unique protein profile compared to neutrophils from healthy age-matched controls. Furthermore, the neutrophil profiles of COPD patients do not reflect putative dominant signals induced by TNFα, GM-CSF or their combination. Our results indicate that systemic neutrophil responses in COPD patients are caused by a unique but subtle interplay between multiple inflammatory signals.COPD is classified by the guidelines of the Global Initiative for Chronic Obstructive Lung Disease, which is based on lung function parameters: forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) [1]. However, it has become increasingly clear that the GOLD classification does not represent the complex local and systemic inflammation in COPD [2-4]. Part of this inflammatory process is the secretion of inflammatory mediators by lung epithelium, alveolar macrophages and other inflammatory cells [5]. These inflammatory mediators affect the local tissue and attract inflammatory cells to the site of inflammation. For instance, alveolar macrophages secrete tumor necrosis