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Published ahead of print on July 11, 2003, doi:10.1164/rccm.200208-794OC

Am. J. Respir. Crit. Care Med., Volume 168, Number 8, October 2003, 968-975

A more recent version of this article appeared on October 15, 2003
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Submitted on August 6, 2002
Accepted on July 4, 2003

Biopsy neutrophilia,chemokine and receptor gene expression in severe exacerbations of COPD

Yusheng Qiu1, Jie Zhu1, Venkata Bandi2, Robert Atmar2, Keith Hattotuwa1, Kay Guntapalli2, and Peter Jeffery1*

1 Lung Patholgy Unit, Gene Therapy Department, National Heart and Lung Institute, Imperial College London, London, London, UK, 2 Pulmonary Critical Care Division, Baylor College of Medicine, Houston, Texas, USA

* To whom correspondence should be addressed. E-mail: p.jeffery{at}ic.ac.uk.

We have applied immunohistology and in situ hybridisation to bronchial biopsies of patients with chronic obstructive pulmonary disease (COPD) in order to examine neutrophil recruitment and to determine neutrophil chemoattractant and CXC receptor (R)-1 and 2 gene expression associated with acute severe exacerbations. Cells were counted in endobronchial biopsies of: 1) patients with chronic obstructive pulmonary disease intubated for exacerbations (E-COPD; n=15), 2) those with COPD in a stable phase of their disease (S-COPD; n=7) and 3) non-smoker surgical controls intubated for a non-respiratory surgical procedure (NSC; n=15). By comparison with the NSC and S-COPD groups, neutrophilia and gene expression for epithelial-derived neutrophil attractant-78 (CXCL5), interleukin-8 (CXCL8), CXCR1 and CXCR2 were each up-regulated in the E-COPD group (p< 0.01); compared with S-COPD, by 97x, 6x, 6x, 3x and 7-fold respectively (p<0.01). In E-COPD, there was a significant positive association between the numbers of neutrophils and CXCR2 (r=0.79; p<0.01) but not CXCR1 mRNA+ cells. At the time of sampling,there was no association between neutrophil number and 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: COPD, neutrophils, chemokines, CXCL5, CXCL8, CXCR1, CXCR2.




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