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Published ahead of print on January 15, 2004, doi:10.1164/rccm.200311-1529OC
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American Journal of Respiratory and Critical Care Medicine Vol 169. pp. 1001-1006, (2004)
© 2004 American Thoracic Society

Hyperplasia of Smooth Muscle in Mild to Moderate Asthma without Changes in Cell Size or Gene Expression

Prescott G. Woodruff, Gregory M. Dolganov, Ronald E. Ferrando, Samantha Donnelly, Steven R. Hays, Owen D. Solberg, Roderick Carter, Hofer H. Wong, Peggy S. Cadbury and John V. Fahy

Division of Pulmonary and Critical Care Medicine, Department of Medicine, and Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California

Correspondence and requests for reprints should be addressed to Prescott G. Woodruff, M.D., M.P.H., Box 0130, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143. E-mail: woodruf{at}itsa.ucsf.edu

Bronchial hyperresponsiveness in mild to moderate asthma may result from airway smooth muscle cell proliferation or acquisition of a hypercontractile phenotype. Because these cells have not been well characterized in mild to moderate asthma, we examined the morphometric and gene expression characteristics of smooth muscle cells in this subgroup of patients with asthma. Using bronchial biopsies from 14 subjects with mild to moderate asthma and 15 control subjects, we quantified smooth muscle cell morphology by stereology and the expression of a panel of genes related to a hypercontractile phenotype of airway smooth muscle, using laser microdissection and two-step real-time polymerase chain reaction. We found that airway smooth muscle cell size was similar in both groups, but cell number was nearly twofold higher in subjects with asthma (p = 0.03), and the amount of smooth muscle in the submucosa was increased 50–83% (p < 0.005). Gene expression profiling in smooth muscle cells showed no difference in the expression of genes encoding phenotypic markers in cells from healthy subjects and subjects with asthma (all p > 0.1). We conclude that airway smooth muscle proliferation is a pathologic characteristic of subjects with mild to moderate asthma. However, smooth muscle cells in mild to moderate asthma do not show hypertrophy or gene expression changes of a hypercontractile phenotype observed in vitro.

Key Words: asthma • airway remodeling • airway smooth muscle • bronchial hyperresponsiveness




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S.-Z. Wang, Y.-X. Bao, C. L. Rosenberger, Y. Tesfaigzi, J. M. Stark, and K. S. Harrod
IL-12p40 and IL-18 Modulate Inflammatory and Immune Responses to Respiratory Syncytial Virus Infection
J. Immunol., September 15, 2004; 173(6): 4040 - 4049.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
J. L. Black
Asthma--More Muscle Cells or More Muscular Cells?
Am. J. Respir. Crit. Care Med., May 1, 2004; 169(9): 980 - 981.
[Full Text] [PDF]


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