ASTHMA

Comparison of gel contraction mediated by airway smooth muscle cells from patients with and without asthma

Hisako Matsumoto¹, Lyn M Moir², Brian G G Oliver¹, Janette K Burgess^1,2, Michael Roth², Judith L Black^1,2, Brent E McParland¹

¹ Discipline of Pharmacology, University of Sydney, NSW 2006, Australia
² Woolcock Institute of Medical Research, Camperdown, NSW 2050, Australia

Correspondence to:
Dr Hisako Matsumoto
Department of Respiratory Medicine, Kyoto University, Kyoto, Japan; hmatsumo{at}kuhp.kyoto-u.ac.jp

Backgrounds: Exaggerated bronchial constriction is the most significant and life threatening response of patients with asthma to inhaled stimuli. However, few studies have investigated the contractility of airway smooth muscle (ASM) from these patients. The purpose of this study was to establish a method to measure contraction of ASM cells by embedding them into a collagen gel, and to compare the contraction between subjects with and without asthma.

Methods: Gel contraction to histamine was examined in floating gels containing cultured ASM cells from subjects with and without asthma following overnight incubation while unattached (method 1) or attached (method 2) to casting plates. Smooth muscle myosin light chain kinase protein levels were also examined.

Results: Collagen gels containing ASM cells reduced in size when stimulated with histamine in a concentration-dependent manner and reached a maximum at a mean (SE) of 15.7 (1.2) min. This gel contraction was decreased by inhibitors for phospholipase C (U73122 [GenBank] ), myosin light chain kinase (ML-7) and Rho kinase (Y27632). When comparing the two patient groups, the maximal decreased area of gels containing ASM cells from patients with asthma was 19 (2)% (n = 8) using method 1 and 22 (3)% (n = 6) using method 2, both of which were greater than that of cells from patients without asthma: 13 (2)% (n = 9, p = 0.05) and 10 (4)% (n = 5, p = 0.024), respectively. Smooth muscle myosin light chain kinase levels were not different between the two groups.

Conclusion: The increased contraction of asthmatic ASM cells may be responsible for exaggerated bronchial constriction in asthma.

Abbreviations: ASM, airway smooth muscle; MLC, myosin light chain; MLCK, myosin light chain kinase; PLC, phospholipase C; ROCK, Rho-associated coiled coil forming kinase; smMLCK, smooth muscle MLCK

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Article

Airwaves

Wisia Wedzicha
Thorax 2007 62: 837. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• Margulis, A., Nocka, K. H., Brennan, A. M., Deng, B., Fleming, M., Goldman, S. J., Kasaian, M. T. (2009). Mast Cell-Dependent Contraction of Human Airway Smooth Muscle Cell-Containing Collagen Gels: Influence of Cytokines, Matrix Metalloproteases, and Serine Proteases. J. Immunol. 183: 1739-1750 [Abstract] [Full Text]  
• Fairbank, N. J., Connolly, S. C., MacKinnon, J. D., Wehry, K., Deng, L., Maksym, G. N. (2008). Airway smooth muscle cell tone amplifies contractile function in the presence of chronic cyclic strain. Am. J. Physiol. Lung Cell. Mol. Physiol. 295: L479-L488 [Abstract] [Full Text]  
• Baroffio, M., Crimi, E., Brusasco, V. (2008). Review: Airway smooth muscle as a model for new investigative drugs in asthma. Ther Adv Respir Dis 2: 129-139 [Abstract]  
• Martin, J. G., Jo, T. (2008). Genetic Differences in Airway Smooth Muscle Function. Proc Am Thorac Soc 5: 73-79 [Abstract] [Full Text]