Proliferative effects of eosinophil lysates on cultured human airway smooth muscle cells

Background: The hypertrophy/hyperplasia of airway smooth muscle (ASM) cells is one of the characteristic features of bronchial asthma. This structural change leads to the thickening of airway walls resulting in the amplification of airway narrowing. However, the pathogenesis of this structural change has not yet been determined. Eosinophils, which play a pathogenic role in asthma, have been demonstrated to have proliferative effects on fibroblasts and vascular smooth muscle cells. Objective: We attempted to investigate the potential of eosinophils to induce the proliferation of ASM cells. Methods: We examined the effect of lysates of eosinophils purified from peripheral blood of healthy donors on cultured human ASM cell proliferation. Results: Eosinophil lysates significantly induced ASM cell proliferation in time- and dose-dependent manners, reaching a maximum on day 6 at 50% of eosinophil lysates (6.0 ± 0.7 × 10⁴ [mean ± SD]/well, n=5 vs. 4.5 ± 1.1 × 10⁴/well, n=5; P< 0.05). This proliferative activity was heatsensitive and recovered in the soluble fraction of the eosinophil lysates. Furthermore, the molecular weight of the mitogenic activity in the soluble fraction was identified as lower than 10kDa. The inhibitory activity to ASM cell proliferation was also found in the insoluble fraction of the lysates. Conclusion: These results indicate that circulating eosinophils store mitogenic activity for ASM cells, suggesting that eosinophils might contribute to the development of the hyperplasia of ASM cells in asthmatics through the release of the stored mitogenic activity upon stimulation at the site of inflammation.