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Am. J. Respir. Crit. Care Med., Volume 164, Number 3, August 2001, 474-477

Airway Smooth Muscle Cell Proliferation Is Increased in Asthma

PETER R. A. JOHNSON, MICHAEL ROTH, MICHAEL TAMM, MARGARET HUGHES, QI GE, GREG KING, JANETTE K. BURGESS, and JUDITH L. BLACK

Departments of Pharmacology and Pharmacy, University of Sydney, Institute of Respiratory Medicine, Royal Prince Alfred Hospital, Sydney, Australia

Increased airway smooth muscle (ASM) within the bronchial wall of asthmatic patients has been well documented and is likely to be the result of increased muscle proliferation. We have for the first time been able to culture ASM cells from asthmatic patients and to compare their proliferation rate with that of nonasthmatic patients. Asthmatic ASM cell cultures (n = 12) were established from explanted lungs and endobronchial biopsies. Nonasthmatic ASM cells (n = 10) were obtained from explanted tissue from patients with no airway disease, emphysema, carcinoma, and fibrosing alveolitis. Cell counts, tritiated thymidine incorporation, and cell cycle analysis were conducted over 7 d. Asthmatic ASM cell numbers at Days 3, 5, and 7 were significantly higher than corresponding values for nonasthmatic cells (p < 0.05). Tritiated thymidine incorporation was increased 3.2-fold in asthmatic cells compared with nonasthmatic cells within the first 24 h (p = 0.026). Flow cytometric analysis of DNA content on Days 1 and 2 revealed that a significantly greater percentage of asthmatic ASM cells were in the G2 + M phase (p < 0.05). This study shows for the first time that proliferation of ASM cells is increased in patients with asthma and provides evidence for an intrinsic abnormality in the ASM cell in this disease.

Keywords: asthma; human airway smooth muscle; cell culture; cell proliferation; hyperplasia




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