title: Increased expression of mRNA encoding RANTES and MCP-3 in the bronchial mucosa in atopic asthma.
abstract: The selective recruitment of eosinophils into the mucosal lining of the airways is a prominent feature of atopic asthma, and is believed to be an important component in the disease pathogenesis. The precise stimuli 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 eosinophil-active chemotactic cytokines, the factor regulated upon activation 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 nonasthmatic (n = 8) and nonatopic nonasthmatic (n = 8) control subjects. In addition, further biopsies from each subject were prepared for immunohistochemistry and the numbers of activated (EG2+) eosinophils measured. The expression of RANTES mRNA was significantly elevated in the atopic asthmatic group as compared to the atopic nonasthmatic controls (p = 0.013) and the nonatopic nonasthmatic controls (p = 0.007). Similarly, the expression 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 RANTES and MCP-3 mRNA expression was associated with significantly increased numbers of bronchial mucosal eosinophils in the atopic asthmatic patients as compared to the atopic nonasthmatic (p = 0.03) and nonatopic nonasthmatic (p = 0.006) control subjects. In conclusion, we have identified 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 role in the mechanism of eosinophil recruitment to the asthmatic bronchial mucosa.
authors.affiliation: National Heart & Lung Institute at Imperial College of Science, Technology & Medicine, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Powell
authors.forename: M
authors.initials: M
authors.lastname: Humbert
authors.forename: S R
authors.initials: SR
authors.lastname: Durham
authors.forename: B
authors.initials: B
authors.lastname: Assoufi
authors.forename: A B
authors.initials: AB
authors.lastname: Kay
authors.forename: C J
authors.initials: CJ
authors.lastname: Corrigan
mesh_terms: D000199:Actins / Q000235:genetics; D000328:Adult; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism; D016022:Case-Control Studies; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D054410:Chemokine CCL7; D016207:Cytokines; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D018945:Monocyte Chemoattractant Proteins / Q000096:biosynthesis*; D009092:Mucous Membrane / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D000199:Actins; C515450:CCL7 protein, human; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D016207:Cytokines; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger