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Increased CCL5 and CXCL7 chemokine expression is associated with neutrophil activation in severe stable COPD
  1. Antonino Di Stefano (antonino.distefano{at}fsm.it)
  1. Fondazione S. Maugeri, IRCCS, Citoimmunopatologia apparato Cardio Respiratorio, Veruno (NO), Italy
    1. Gaetano Caramori
    1. Centro di Ricerca su Asma e BPCO, Università di Ferrara, Italy
      1. Isabella Gnemmi
      1. Fondazione S. Maugeri, IRCCS, Citoimmunopatologia apparato Cardio Respiratorio, Veruno (NO), Italy
        1. Marco Contoli
        1. Centro di Ricerca su Asma e BPCO, Università di Ferrara, Italy
          1. Laura Bristot
          1. Centro di Ricerca su Asma e BPCO, Università di Ferrara, Italy
            1. Armando Capelli
            1. Fondazione S. Maugeri, IRCCS, Divisione di Pneumologia, Veruno (NO), Italy
              1. Fabio L Ricciardolo
              1. Department of Pulmonary Disease, University of Torino, Italy
                1. Francesca Magno
                1. Fondazione S. Maugeri, IRCCS, Citoimmunopatologia apparato Cardio Respiratorio, Veruno (NO), Italy
                  1. Silvestro E D'Anna
                  1. Fondazione S. Raffaele, IRCCS, Divisione di Pneumologia, Cefalù (PA), Italy
                    1. Andrea Zanini
                    1. Fondazione S. Maugeri, IRCCS, Divisione di Pneumologia, Tradate, Italy
                      1. Marco Carbone
                      1. Fondazione S. Maugeri, IRCCS, Citoimmunopatologia apparato Cardio Respiratorio, Veruno (NO), Italy
                        1. Federica Sabatini
                        1. Gaslini Institute, IRCCS, Unit of Respiratory Disease, Genova, Italy
                          1. Cesare Usai
                          1. Istituto di Cibernetica e Biofisica CNR, Genova, Italy
                            1. Paola Brun
                            1. Department of Histology, Microbiology and Medica Biotechnology, University of Padova, Italy
                              1. Kian Fan Chung
                              1. Airways Disease Section, National Heart and Lung Institute, Imperial College London, United Kingdom
                                1. Peter J Barnes
                                1. Airways Disease Section, National Heart and Lung Institute, Imperial College London, United Kingdom
                                  1. Alberto Papi
                                  1. Centro di Ricerca su Asma e BPCO, Università di Ferrara, Italy
                                    1. Ian Adcock
                                    1. Airways Disease Section, National Heart and Lung Institute, Imperial College London, United Kingdom
                                      1. Bruno Balbi
                                      1. Fondazione S. Maugeri, IRCCS, Divisione di Pneumologia, Veruno (NO), Italy

                                        Abstract

                                        Background: Increased numbers of activated neutrophils have been reported in the bronchial mucosa of stable COPD patients, particularly in severe disease.

                                        Objectives: To investigate the expression of neutrophilic chemokines and adhesion molecules in bronchial biopsies from patients with stable COPD of different severity (GOLD stage 1 to 4) compared with age-matched control subjects, smokers with normal lung function and never smokers.

                                        Methods: The expression of CCL5, CXCL1, 5, 6, 7 and 8, CXCR1, CXCR2, CD11b and CD44 was measured in the bronchial mucosa using immunohistochemistry, confocal immunofluorescence, real time quantitative polymerase chain reaction (RT-QPCR) and Western blotting (WB).

                                        Results: Numbers of CCL5+ epithelial cells and CCL5+ and CXCL7+ immunostained cells are increased in the bronchial submucosa of stable severe COPD patients compared with control never smokers and smokers with normal lung function. This is also confirmed at the level of mRNA expression. The numbers of CCL5+ cells in the submucosa of COPD were 2-15 times higher compared to any other chemokines. There was no correlation between the number of these cells and the number of neutrophils in the bronchial submucosa. Compared to control smokers, the percentage of neutrophils coexpressing CD11b and CD44 receptors was significantly increased in the submucosa of patients with COPD.

                                        Conclusion: The increased expression of CCL5 and CXCL7 in the bronchial mucosa of stable COPD patients, together with an increased expression of extracellular matrix-binding receptors on neutrophils, may be involved in the pathogenesis of COPD.

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