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Published ahead of print on July 11, 2003, doi:10.1164/rccm.200208-794OC
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American Journal of Respiratory and Critical Care Medicine Vol 168. pp. 968-975, (2003)
© 2003 American Thoracic Society

Biopsy Neutrophilia, Neutrophil Chemokine and Receptor Gene Expression in Severe Exacerbations of Chronic Obstructive Pulmonary Disease

Yusheng Qiu, Jie Zhu, Venkata Bandi, Robert L. Atmar, Keith Hattotuwa, Kay K. Guntupalli and Peter K. Jeffery

Lung Pathology, Department of Gene Therapy, Imperial College, Royal Brompton Hospital, London, United Kingdom; and Department of Medicine and Department of Molecular Virology and Microbiology, Baylor College of Medicine, Ben Taub General Hospital, Houston, Texas

Correspondence and requests for reprints should be addressed to Peter K. Jeffery, F.R.C.Path, D.Sc., Ph.D., Lung Pathology, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK. E-mail: p.jeffery{at}ic.ac.uk

We have applied immunohistology and in situ hybridization to bronchial biopsies of patients with chronic obstructive pulmonary disease (COPD) to examine neutrophil recruitment and to determine neutrophil chemoattractant and CXC receptor (CXCR) 1 and CXCR2 gene expression associated with acute severe exacerbations. Cells were counted in endobronchial biopsies of (1) patients with COPD intubated for exacerbations (E-COPD; n = 15), (2) those with COPD in a stable phase of their disease (S-COPD; n = 7), and (3) nonsmoker surgical control subjects intubated for a nonrespiratory surgical procedure (n = 15). In comparison with the nonrespiratory surgical procedure and S-COPD groups, neutrophilia and gene expression for epithelial-derived neutrophil attractant-78 (CXCL5), interleukin-8 (CXCL8), CXCR1, and CXCR2 were each upregulated in the E-COPD group (p < 0.01); compared with the S-COPD group, by 97-, 6-, 6-, 3-, and 7-fold, respectively (p < 0.01). In E-COPD, there was a significant positive association between the number of neutrophils and CXCR2 mRNA–positive cells (r = 0.79; p < 0.01) but not between the number of neutrophils and CXCR1 mRNA–positive cells. At the time of sampling of the mucosa, there was no association between neutrophil number and either the length of intubation or viral infection. Thus, in COPD, in addition to CXCL8 and CXCR1, CXCL5 and CXCR2 appear to play important roles in the airway neutrophilia characteristic of severe exacerbations.

Key Words: chemokines • CXCL5, CXCL8, CXCR1, CXCR2 • COPD • neutrophils




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