Increased expression of mRNA encoding RANTES and MCP-3 in the bronchial mucosa in atopic asthma

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.

This article has been cited by other articles:

				X.-Z. Shang, B.-C. Chiu, V. Stolberg, N. W. Lukacs, S. L. Kunkel, H. S. Murphy, and S. W. Chensue Eosinophil Recruitment in Type-2 Hypersensitivity Pulmonary Granulomas : Source and Contribution of Monocyte Chemotactic Protein-3 (CCL7) Am. J. Pathol., July 1, 2002; 161(1): 257 - 266. [Abstract] [Full Text] [PDF]

				E M Glare, M Divjak, M J Bailey, and E H Walters The usefulness of competitive PCR: airway gene expression of IL-5, IL-4, IL-4{delta}2, IL-2, and IFN{gamma} in asthma Thorax, July 1, 2001; 56(7): 541 - 548. [Abstract] [Full Text] [PDF]

				K. Blease, B. Mehrad, N. W. Lukacs, S. L. Kunkel, T. J. Standiford, and C. M. Hogaboam Antifungal and Airway Remodeling Roles for Murine Monocyte Chemoattractant Protein-1/CCL2 During Pulmonary Exposure to Asperigillus fumigatus Conidia J. Immunol., February 1, 2001; 166(3): 1832 - 1842. [Abstract] [Full Text] [PDF]

				C. Stellato, S. Matsukura, A. Fal, J. White, L. A. Beck, D. Proud, and R. P. Schleimer Differential Regulation of Epithelial-Derived C-C Chemokine Expression by IL-4 and the Glucocorticoid Budesonide J. Immunol., November 15, 1999; 163(10): 5624 - 5632. [Abstract] [Full Text] [PDF]

				J. L. Pype, L. J. Dupont, P. Menten, E. Van Coillie, G. Opdenakker, J. Van Damme, K. Fan Chung, M. G. Demedts, and G. M. Verleden Expression of Monocyte Chemotactic Protein (MCP)-1, MCP-2, and MCP-3 by Human Airway Smooth-Muscle Cells . Modulation by Corticosteroids and T-Helper 2 Cytokines Am. J. Respir. Cell Mol. Biol., October 1, 1999; 21(4): 528 - 536. [Abstract] [Full Text]

				T. W. Wright, C. J. Johnston, A. G. Harmsen, and J. N. Finkelstein Chemokine Gene Expression during Pneumocystis carinii-Driven Pulmonary Inflammation Infect. Immun., July 1, 1999; 67(7): 3452 - 3460. [Abstract] [Full Text] [PDF]

				J Wedemeyer, A Lorentz, M Goke, P N Meier, P Flemming, C A Dahinden, M P Manns, and S C Bischoff Enhanced production of monocyte chemotactic protein 3 in inflammatory bowel disease mucosa Gut, May 1, 1999; 44(5): 629 - 635. [Abstract] [Full Text] [PDF]

				O. Ayad, J. M. Stark, M. M. Fiedler, I. Y. Menendez, M. A. Ryan, and H. R. Wong The Heat Shock Response Inhibits RANTES Gene Expression in Cultured Human Lung Epithelium J. Immunol., September 1, 1998; 161(5): 2594 - 2599. [Abstract] [Full Text] [PDF]