Tryptase's potent mitogenic effects in human airway smooth muscle cells are via nonproteolytic actions.
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.
Brown
James K
JK
Pulmonary and Critical Care Medicine Section, Medical Service, Department of Veterans Affairs Medical Center, San Francisco, CA 94121, USA. jkbrown@itsa.ucsf.edu
Jones
Cary A
CA
Rooney
Leeann A
LA
Caughey
George H
GH
Hall
Ian P
IP
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D000077214:Becaplermin; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D053818:Chymases; D004247:DNA / Q000096:biosynthesis; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005174:Factor XII / Q000494:pharmacology; D015951:Factor Xa / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006490:Hemostatics / Q000494:pharmacology; D006801:Humans; D006965:Hyperplasia; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008407:Mast Cells / Q000201:enzymology / Q000276:immunology; D008934:Mitogens / Q000378:metabolism* / Q000494:pharmacology; D009130:Muscle, Smooth / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000032:analysis; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000235:genetics; D012697:Serine Endopeptidases / Q000378:metabolism* / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D014132:Trachea / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D053802:Tryptases
D000925:Anticoagulants; D006490:Hemostatics; D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D005174:Factor XII; D004247:DNA; D012697:Serine Endopeptidases; D053818:Chymases; D013917:Thrombin; D053802:Tryptases; D015951:Factor Xa