Alveolar macrophages as orchestrators of COPD.
Alveolar macrophages play a critical role in the pathophysiology of COPD and are a major target for future anti-inflammatory therapy. Macrophage numbers are markedly increased in the lung and alveolar space of patients with COPD and are localized to sites of alveolar destruction. The increased numbers of macrophages may result from increased recruitment of blood monocytes, prolonged survival in the lung and to a lesser extent to increased proliferation in the lung. Alveolar macrophages from COPD patients have an increased baseline and stimulated secretion of inflammatory proteins, including certain cytokines, chemokines, reactive oxygen species and elastolytic enzymes, which together could account for all of the pathophysiological features of COPD. Alveolar macrophages form COPD appear to be resistant to the anti-inflammatory effects of corticosteriods and this is linked to reduced activity and expression of histone deacetylase 2, a nuclear enzyme that switches off inflammatory genes activated through the transcription factor nuclear factor-KB. Alternative anti-inflammatory therapies that inhibit macrophages are therefore needed in the future to deal with the chronic inflammation of COPD. These drugs may include resveratrol, theophylline derivatives, MAP kinase inhibitors and phosphodiesterase-4 inhibitors.
Barnes
Peter J
PJ
National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse St., SW3 6LY, London, UK. p.j.barnes@ic.ac.uk
D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D010586:Phagocytes / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D014665:Vasodilator Agents / Q000494:pharmacology
D036341:Intercellular Signaling Peptides and Proteins; D010726:Phosphodiesterase Inhibitors; D014665:Vasodilator Agents; D010447:Peptide Hydrolases