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Am J Physiol Lung Cell Mol Physiol 282: L197-L206, 2002;
1040-0605/02 $5.00
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Vol. 282, Issue 2, L197-L206, February 2002

EDITORIAL FOCUS
Tryptase's potent mitogenic effects in human airway smooth muscle cells are via nonproteolytic actions

James K. Brown1,2, Cary A. Jones1, Leeann A. Rooney1, George H. Caughey2, and Ian P. Hall3

1 Pulmonary and Critical Care Medicine Section, Medical Service, Department of Veterans Affairs Medical Center, San Francisco 94121; 2 Cardiovascular Research Institute and Department of Medicine, University of California, San Francisco, CA 94143-0911; and 3 Division of Therapeutics, University Hospital, Nottingham NG7 2UH, United Kingdom

We reported previously that mast cell tryptase is a growth factor for dog tracheal smooth muscle cells. The goals of our current experiments were to determine if tryptase also is mitogenic in cultured human airway smooth muscle cells, to compare its strength as a growth factor with that of other mitogenic serine proteases, and to determine whether its proteolytic actions are required for mitogenesis. Highly purified preparations of human lung beta -tryptase (1-30 nM) caused dose-dependent increases in DNA synthesis in human airway smooth muscle cells. Maximum tryptase-induced increases in DNA synthesis far exceeded those occurring in response to coagulation cascade proteases, such as thrombin, factor Xa, or factor XII, or to other mast cell proteases, such as chymase or mastin. Irreversibly abolishing tryptase's catalytic activity did not alter its effects on increases in DNA synthesis. We conclude that beta -tryptase is a potent mitogenic serine protease in cultured human airway smooth muscle cells. However, its growth stimulatory effects in these cells occur predominantly via nonproteolytic actions.

mast cell proteases; serine proteases; airway smooth muscle hyperplasia; noncatalytic effects of proteases


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