Neutrophil chemokine receptor (CXCR1 and 2) gene expression and biopsy neutrophilia in severe exacerbations of chronic obstructive pulmonary disease (COPD)
Y. S. Qiu, J. Zhu, V. Bandi, A. E. Fraire, K. K. Guntapalli, P. K. Jeffery (London, United Kingdom; Texas, Boston, United States Of America)
Source: Annual Congress 2001 - Inflammation and genetics in airway disease
Session: Inflammation and genetics in airway disease
Session type: Oral Presentation
Number: 3386
Disease area: Airway diseases
Abstract Up-regulation of IL-8 and its receptors CXCR1 & 2 is considered to be important to the recruitment of airway mucosal neutrophils in exacerbations of COPD. However, data to support this hypothesis are lacking. We have applied in situ hybridisation to bronchial biopsy tissue to quantify cells expressing mRNA for either CXCR1 or 2 and immunohistochemistry to identify neutrophils by neutrophil elastase. The biopsies were obtained from 16 patients intubated for a severe exacerbation of COPD (Int-COPD), 9 subjects with mild stable COPD (Stable-COPD) and 18 normal healthy non-smokers (NH-NS). The table shows the numbers of positive cells as median (range) per mm2 of subepithelium:
Patient group CXCR1+ cells CXCR2+ cells Neutrophils NH-NS (n=18) 27.8 (0-577) 14.6 (0-248) 0 (0-12) Stable-COPD (n=9) 33.2 (5-245) 12.3 (5-126) 0.6 (0-7) Int-COPD (n=16) 79.1 (12-344)* 69.8 (0-591)* 68.2 (0-594)*
* p<0.01 compared to NH-NS and the stable-COPD groups (Mann-Whitney U test). The intensity of CXCR2 mRNA expression within the cells were stronger than that of CXCR1.There was a significant association between the numbers of neutrophils and CXCR2+ cells (r =0.79; p <0.01; Spearman rank correlation) which was not seen with CXCR1+ cells (r =0.47; p =0.08). In conclusion, significantly increased numbers of neutrophils are recruited to the airway mucosa in severe exacerbations of COPD and this is associated with an up-regulation of both CXCR1 & 2. Funding: Glaxo-Wellcome R&D, UK.
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Y. S. Qiu, J. Zhu, V. Bandi, A. E. Fraire, K. K. Guntapalli, P. K. Jeffery (London, United Kingdom; Texas, Boston, United States Of America). Neutrophil chemokine receptor (CXCR1 and 2) gene expression and biopsy neutrophilia in severe exacerbations of chronic obstructive pulmonary disease (COPD). Eur Respir J 2001; 16: Suppl. 31, 3386
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