Mechanisms of allergyExtracellular matrix proteins modulate asthmatic airway smooth muscle cell proliferation via an autocrine mechanism☆
Section snippets
Cell culture
We obtained human ASM cells from 23 nonasthmatic (50±20 years; mean±SD) and 14 asthmatic (42±16 years; mean±SD) patients by methods adapted from those previously described.15., 16. The characteristics of the patients are listed in Table I. Approval for all experiments with human lung was provided by the Human Ethics Committee of the University of Sydney and the Central Sydney Area Health Service. ASM cell characteristics were determined by immunofluorescence and light microscopy as previously
ECM composition in ASM cells
After 7 days of growth in the presence of 10% serum, the nonasthmatic and asthmatic ASM cells produced varying amounts of the 15 ECM proteins examined. When nonasthmatic and asthmatic ASM cells were compared, a significant increase was observed in perlecan (7.9%±1.5% nonasthmatic and 12.0%±1.1% asthmatic, P<.05, n = 6 and 6, respectively, ANOVA factorial) and collagen type I (3.0%±0.5% nonasthmatic and 8.5%±0.9% asthmatic, P<.05, n = 6 and 6, respectively, ANOVA factorial) (Fig 1). In contrast, a
Discussion
In this study, we have shown that when ASM cells from asthmatic and nonasthmatic patients are compared, cells from asthmatic patients produce increased relative amounts of the structural protein collagen I, the basement membrane protein perlecan, and decreased amounts of the structural protein collagen IV, the glycosaminoglycan chondroitin sulfate, and the basement membrane protein laminin α1. These changes in ECM production are the result of posttranscriptional effects, as there were no
Acknowledgements
We acknowledge the collaborative effort of the cardiopulmonary transplant team and pathologists at St Vincent's Hospital, Sydney. We thank Dr Greg King from the Woolcock Institute of Medical Research,3 Royal Prince Alfred Hospital, Sydney, Australia, for the supply of lung biopsy specimens.
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Supported by the NHMRC, Australia, and Astra Zeneca, Switzerland, and the Rebecca L. Cooper Foundation. Drs Johnson and Burgess contributed equally to this work.