Bronchial mucosal inflammation and up-regulation of CXC chemoattractants and receptors in severe exacerbations of asthma

Yusheng Qiu ¹, Jie Zhu ¹, Venkata Bandi ², Kay K Guntupalli ² and Peter K Jeffery ^3*

¹ Imperial College London, United Kingdom
² Taub General Hospital, United States
³ Imperial College, United Kingdom

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

Accepted 11 November 2006

Abstract

Background: We test the hypothesis that severe exacerbations of asthma are characterised by increased bronchial mucosal neutrophilia associated with up- regulation of neutrophil chemoattractant ligands and their specific cell surface receptors.

Methods: Immunohistology and in situ hybridization were applied to endobronchial biopsies of three groups: (1) 15 patients hospitalised for a severe exacerbation of asthma (E-asthma), (2) 15 with stable asthma (S-asthma) and (3) 15 non-atopic and non-smoker surgical controls (NSC).

Results: Neutrophils and eosinophils were significantly more frequent in both the epithelium and subepithelium of E-asthma (median values: neutrophils: 7 (0-380)and 78(2-898) mm-2, eosinophils: 31 (0-167) and 60 (6-351) mm-2, p 0.01 compared with NSC:, 0 (0-10, 0-7, 0-18 and 0-3) mm-2, respectively), resulting in similar final densities of eosinophils and neutrophils. In respect of neutrophil chemoattractants and receptors, counts of CXCL5, CXCL8, CXCR1 and CXCR2 mRNA positive cells in the subepithelium of the E-asthma group were 5, 4, 4 and 18 times greater, respectively, (p 0.01) than that of the NSC group. In E-asthma, cells expressing CXCL5 or CXCR2 were 8- and 3-fold more frequent than those expressing CXCL8 or CXCR1 mRNA, respectively, (p<0.01). CXCL5 and CXCR2 in E-asthma were associated with the number of eosinophils (r=0.59 and 0.66, p<0.02 for both) rather than with neutrophils.

Conclusion: In severe exacerbations of asthma there is a bronchial mucosal neutrophilia, eosinophilia and up-regulation of CXC chemoattractants and their receptors: CXCL5 and CXCR2 show an association with eosinophila only, and these represent potentially new targets for treatment in exacerbations of asthma.

Keywords: asthma, chemoattractants, exacerbations, inflammation, neutrophils

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