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Am. J. Respir. Cell Mol. Biol., Volume 24, Number 6, June, 2001 682-687

Eotaxin-3 but Not Eotaxin Gene Expression Is Upregulated in Asthmatics 24 Hours after Allergen Challenge

Neville Berkman, Shaul Ohnona, Fan K. Chung, and Raphael Breuer

Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonology, Hadassah University Hospital and the Hebrew University-Hadassah Medical School, Jerusalem, Israel; and National Heart and Lung Institute, London, United Kingdom

Eotaxin is an important mediator of eosinophil recruitment and activation in the airways of asthmatics. Eotaxin-2 and eotaxin-3 are two recently identified chemokines with activity similar to that of eotaxin. Using quantitative polymerase chain reaction analysis, we determined the messenger RNA (mRNA) expression of eotaxin, eotaxin-2, and eotaxin-3 relative to GAPDH mRNA expression in bronchial biopsies and bronchoalveolar lavage fluid (BALF) cells obtained from subjects with mild asthma, asthmatic subjects 24 h after allergen challenge, and normal control subjects. In bronchial biopsies, gene expression was upregulated in asthmatic subjects as compared with control subjects for eotaxin (log median values 3.18 pg/µg, 95% confidence interval [CI]; 2.27 to 3.79 versus 4.37 pg/µg, 95% CI; 3.97 to 4.65, P = 0.003) and for eotaxin-2 (0.82 pg/µg, 95% CI; 0.08 to 1.72 versus 2.97 pg/µg, 95% CI; 1.97 to 3.45, P = 0.006), but no further increase was observed after allergen challenge. In contrast, eotaxin-3 mRNA expression was not increased in asthmatic compared with control subjects, but was dramatically enhanced 24 h after challenge (median log value 1.93 pg/µg, 95% CI; 0.74 to 3.92 versus 4.62 pg/µg, 95% CI; 3.05 to 6.23, P = 0.036). No significant difference between groups was observed in BALF cell gene expression for any of the chemokines examined. These data suggest that eotaxin-3 rather than eotaxin or eotaxin-2 may account for the ongoing eosinophil recruitment to asthmatic airways in the later stages (24 h) following allergen challenge.


Abbreviations: bronchoalveolar lavage, BAL; BAL fluid, BALF; base pairs, bp; CC-chemokine receptor, CCR; complementary DNA, cDNA; confidence interval, CI; forced expiratory volume in 1 s, FEV1; glyceraldehyde-3-phosphate dehydrogenase, GAPDH; messenger RNA, mRNA; provocative concentration causing a 20% fall in FEV1, PC20; polymerase chain reaction, PCR.




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