Published ahead of print on March 4, 2004, doi:10.1164/rccm.200306-855OC Am. J. Respir. Crit. Care Med., Volume 169, Number 10, May 2004, 1110-1117 A more recent version of this article appeared on May 15, 2004
Submitted on June 27, 2003 Contribution of Eotaxin-1 to Eosinophil Chemotactic Activity of Moderate and Severe Asthmatic SputumGordon Dent1*,1 Respiratory Cell and Molecular Biology, Division of Infection, Inflammation and Repair, University of Southampton School of Medicine, Southampton, United Kingdom, 2 Cambridge Antibody Technology, Milstein Building, Cambridge, United Kingdom, 3 Department of Pneumology and Allergology, University of Liege, Faculty of Medicine, Liege, Belgium * To whom correspondence should be addressed. E-mail: g.dent{at}hfac.keele.ac.uk.
The CC chemokine, eotaxin-1 (CCL11) is chemotactic for eosinophils, basophils and Th2 cells and may play a role in allergic inflammation. We investigated its contribution as an eosinophil chemoattractant in asthmatic airway secretions (sampled as induced sputum), which possess chemotactic activity for eosinophils and T cells. Sputum samples collected from healthy subjects and mild, stable-moderate, unstable-moderate and severe asthmatics were processed with phosphate-buffered saline and assayed for eotaxin by ELISA and eosinophil chemotactic activity in a fluorescence-based chemotaxis assay. The contribution of eotaxin to chemotactic activity was studied by using a high-affinity neutralizing human anti-eotaxin antibody, CAT-213. Sputum eotaxin concentration was significantly raised in moderate and severe asthma (P<0.05 vs. healthy controls) but not mild asthma. Chemotactic activity was significantly increased over healthy subjects in all asthmatic groups (P<0.05) and was significantly inhibited by CAT-213 (100 nM) in moderate and severe asthmatics, with median inhibition of 52% (P<0.05), 78% (P<0.0001) and 86% (P<0.0001) in stable-moderate, unstable-moderate and severe asthmatic samples, respectively. Eotaxin contributes to the eosinophil chemotactic activity of sputum from subjects with more severe forms of asthma but not mild asthma, suggesting that its contribution is more important in more severe disease. This activity is inhibited significantly by CAT-213. Key words: Antibodies, asthma, chemokines, chemotaxis
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