Neutrophils in Chronic Obstructive Pulmonary Disease

  1. Derek Chadwick Organizer and
  2. Jamie A. Goode
  1. Timothy J. Williams and
  2. Peter J. Jose

Published Online: 7 OCT 2008

DOI: 10.1002/0470868678.ch9

Chronic Obstructive Pulmonary Disease: Pathogenesis to Treatment: Novartis Foundation Symposium 234

Chronic Obstructive Pulmonary Disease: Pathogenesis to Treatment: Novartis Foundation Symposium 234

How to Cite

Williams, T. J. and Jose, P. J. (2000) Neutrophils in Chronic Obstructive Pulmonary Disease, in Chronic Obstructive Pulmonary Disease: Pathogenesis to Treatment: Novartis Foundation Symposium 234 (eds D. Chadwick and J. A. Goode), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/0470868678.ch9

Author Information

  1. Leukocyte Biology Section, Biomedical Sciences Division, Sir Alexander Fleming Building, Imperial College School of Medicine, London SW7 2AZ, UK

Publication History

  1. Published Online: 7 OCT 2008
  2. Published Print: 28 NOV 2000

Book Series:

  1. Novartis Foundation Symposia

Book Series Editors:

  1. Novartis Foundation

ISBN Information

Print ISBN: 9780471494379

Online ISBN: 9780470868676

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Summary

Neutrophil accumulation in the lung is a prominent feature of chronic obstructive pulmonary disease (COPD) and the activation of these cells, producing proteases and oxygen-derived free radicals, is thought to be important in the pathogenesis of the disease. An important step in recruitment is the local generation of a neutrophil chemoattractant signal which mediates the trapping and firm adhesion of rolling neutrophils on the microvascular endothelium, followed by migration via intercellular junctions. Two neutrophil chemoattractants are particularly important in this respect, C5a generated by cleavage of complement C5 in interstitial fluid, and interleukin (IL)-8 synthesized by cells in the lung, e.g. macrophages, epithelial cells, endothelial cells, smooth muscle cells and neutrophils themselves. Lipid mediators, such as leukotriene B4 (LTB4), are also potentially important. Several studies have been carried out to investigate the role of IL-8 in COPD. IL-8 has been detected in bronchoalveolar lavage fluid and sputum from such subjects and in the systemic circulation. The levels of IL-8 have been found to correlate with neutrophil numbers and markers of neutrophil activation, such as myeloperoxidase activity. Some studies have also found a correlation between IL-8 levels, neutrophil numbers and the degree of lung dysfunction. These parameters are insensitive to steroids. Thus, the mechanisms involved in neutrophil recruitment, i.e. chemoattractant secretion or action, adhesion and endothelial transmigration, are important potential targets for the development of novel therapy. The IL-8 receptors on neutrophils, CXCR1 and CXCR2, are of particular interest.