INCREASED EXPRESSION OF MESSENGER-RNA ENCODING RANTES AND MCP-3 IN THE BRONCHIAL-MUCOSA IN ATOPIC ASTHMA

The selective recruitment of eosinophils into the mucosal lining of th e airways is a prominent feature of atopic asthma, and is believed to be an important component in the disease pathogenesis, The precise sti muli responsible for the influx of eosinophils remain unclear, Using a semiquantitative reverse transcriptase polymerase chain reaction (RT- PCR) technique, the numbers of copies (relative to the ''housekeeping' ' gene beta-actin) of messenger ribonucleic acid (mRNA) encoding the e osinophil-active chemotactic cytokines, the factor regulated upon acti vation in normal T-cells expressed and secreted (RANTES) and monocyte chemotactic protein-3 (MCP-3), was measured in bronchial biopsies from atopic asthmatic patients (n=9), and compared with atopic nonasthmati c (n=8) and nonatopic nonasthmatic (n=8) control subjects, In addition , further biopsies from each subject were prepared for immunohistochem istry and the numbers of activated (EG2+) eosinophils measured. The ex pression of RANTES mRNA was significantly elevated in the atopic asthm atic group as compared to the atopic nonasthmatic controls (p=0.013) a nd the nonatopic nonasthmatic controls (p=0.007). Similarly, the expre ssion of mRNA encoding MCP-3 was significantly elevated in the atopic asthmatic group, relative to the atopic nonasthmatic controls (p=0.014 ) and the nonatopic nonasthmatic control group (p=0.011), Elevated RAN TES and MCP-3 mRNA expression was associated with significantly increa sed numbers of bronchial mucosal eosinophils in the atopic asthmatic p atients as compared to the atopic nonasthmatic (p=0.03) and nonatopic nonasthmatic (p=0.006) control subjects. In conclusion, we have identi fied elevated expression of messenger ribonucleic acid encoding RANTES and monocyte chemotactic protein-3 in the bronchial mucosa of atopic asthmatic patients relative to controls, These findings are compatible with the hypothesis that eosinophil-active beta-chemokines play a rol e in the mechanism of eosinophil recruitment to the asthmatic bronchia l mucosa.