Tryptase and agonists of PAR-2 induce the proliferation of human airway smooth
muscle cells.
Berger, Patrick, Diahn-Warng Perng, Hiran Thabrew, Steven J. Compton, Jennifer A
Cairns, Alan R. McEuen, Roger Marthan, José-Manuel Tunon De Lara, and Andrew F.
Walls.
1Immunopharmacology Group, Southampton General Hospital, Southampton SO16
6YD, United Kingdom; and 2Laboratoire de Physiologie Cellulaire Respiratoire, Inserm
E9937, Université Victor Ségalen Bordeaux2, Bordeaux, France
APStracts 8:0337A, 2001.
Airway remodeling with smooth muscle cell (SMC) hyperplasia is a feature of chronic
asthma. We investigated the potential for tryptase, the major secretory product of human
mast cells, to act as a growth factor for human airway SMCs. Because this serine protease
can activate proteinase-activated receptor-2 (PAR-2), we also examined the actions of
SLIGKV, a peptide agonist of PAR-2. Incubation with lung tryptase provoked a twofold
increase in [3H]thymidine incorporation; a similar increase in cell numbers was found
when we used the MTS assay. The effect was catalytic site dependent, being abolished by
the protease inhibitors leupeptin and benzamidine and by heat inactivation of the enzyme.
Tryptase-induced DNA synthesis was inhibited by preincubation of the cells with
pertussis toxin, calphostin C, or genistein. Transduction mechanisms are thus likely to
involve a pertussis toxin-sensitive G protein, protein kinase C, and tyrosine kinase.
SLIGKV elicited a response on SMCs similar to that of tryptase. Tryptase could provide
an important stimulus for SMC proliferation in asthmatic airways, by acting on PAR-2.
Received 20 February 2001; accepted in final form 21 June 2001
APS Manuscript Number A172-1.
Article publication pending J Appl Physiol
ISSN 1080-4757 Copyright 2001 The American Physiological Society.
Published in APStracts on 29 June 2001