Fibrinogenolysis by Human Lung Mast Cell Tryptase
Document Type
Article
Publication Date
1-1-1996
Description
Tryptases are 31 kDa, glycosylated, trypsin-like enzymes that are stored in and released from mast cell granules. Tryptases exist as tetramers and bind heparin, which stabilizes their activity, but they are not inhibited by blood plasma proteinase inhibitors, such as antithrombin III and a1-proteinase inhibitor. Tryptases appear to serve a limited proteolytic function, cleaving substrates such as high molecular weight kininogen, vasoactive intestinal peptide and fibrinogen. Research in this laboratory is focusing on the mechanism by which human lung mast cell tryptase modifies the structure of fibrinogen to prevent thrombin from converting it to a fibrin clot. SDS-PAGE of cleavage products shows that tryptase cleaves the alpha subunit of fibrinogen first, followed by cleavage of the beta subunit. The alpha subunit of fibrinogen is reduced in size by approximately 15 kDa and amino acid sequence analysis of this fragment indicates that cleavage occurs in the carboxyl terminal region. Experiments to isolate and sequence the alpha chain's carboxyl terminal fragment are in progress. The Lys21-Lys22 bond is cleaved in the beta subunit. Tryptase competes with thrombin for fibrinogen and appears to augment the inhibition of clotting by heparin in the vacinity of mast cells. These data demonstrate the potential of tryptase to function as an anti-coagulant by destroying fibrinogen. When present findings are combined with previous data showing that tryptase can contribute to fibrinolysis by activating single-chain urinary-type plasminogen activator (Stack and Johnson, J. Biol. Chem. 269, 9416, 1994), it seems that mast cell tryptase may play a significant role in hemostasis.
Citation Information
Johnson, David A.; Carpenter, Marcus D.; and Vanessa, A.. 1996. Fibrinogenolysis by Human Lung Mast Cell Tryptase. Fibrinolysis. Vol.10(SUPPL. 3). 124. https://doi.org/10.1016/s0268-9499(96)80512-1 ISSN: 0268-9499