The tryptase, mouse mast cell protease 7, exhibits anticoagulant activity in vivo and in vitro due to its ability to degrade fibrinogen in the presence of the diverse array of protease inhibitors in plasma - PubMed (original) (raw)

. 1997 Dec 12;272(50):31885-93.

doi: 10.1074/jbc.272.50.31885.

Affiliations

• PMID: 9395536
• DOI: 10.1074/jbc.272.50.31885

Free article

The tryptase, mouse mast cell protease 7, exhibits anticoagulant activity in vivo and in vitro due to its ability to degrade fibrinogen in the presence of the diverse array of protease inhibitors in plasma

C Huang et al. J Biol Chem. 1997.

Free article

Abstract

Mouse mast cell protease (mMCP) 7 is a tryptase of unknown function expressed by a subpopulation of mast cells that reside in numerous connective tissue sites. Because enzymatically active mMCP-7 is selectively released into the plasma of V3 mastocytosis mice undergoing passive systemic anaphylaxis, we used this in vivo model system to identify a physiologic substrate of the tryptase. Plasma samples taken from V3 mastocytosis mice that had been sensitized with immunoglobulin (Ig) E and challenged with antigen were found to contain substantial amounts of four 34-55-kDa peptides, all of which were derived from fibrinogen. To confirm the substrate specificity of mMCP-7, a pseudozymogen form of the recombinant tryptase was generated that could be activated after its purification. The resulting recombinant mMCP-7 exhibited potent anticoagulant activity in the presence of normal plasma and selectively cleaved the alpha-chain of fibrinogen to fragments of similar size as that seen in the plasma of the IgE/antigen-treated V3 mastocytosis mouse. Subsequent analysis of a tryptase-specific, phage display peptide library revealed that recombinant mMCP-7 preferentially cleaves an amino acid sequence that is nearly identical to that in the middle of the alpha-chain of rat fibrinogen. Because fibrinogen is a physiologic substrate of mMCP-7, this tryptase can regulate clot formation and fibrinogen/integrin-dependent cellular responses during mast cell-mediated inflammatory reactions.

PubMed Disclaimer

Similar articles

• Mechanism for activation of mouse mast cell tryptase: dependence on heparin and acidic pH for formation of active tetramers of mouse mast cell protease 6.
  Hallgren J, Karlson U, Poorafshar M, Hellman L, Pejler G. Hallgren J, et al. Biochemistry. 2000 Oct 24;39(42):13068-77. doi: 10.1021/bi000973b. Biochemistry. 2000. PMID: 11041873
• Formation of enzymatically active, homotypic, and heterotypic tetramers of mouse mast cell tryptases. Dependence on a conserved Trp-rich domain on the surface.
  Huang C, Morales G, Vagi A, Chanasyk K, Ferrazzi M, Burklow C, Qiu WT, Feyfant E, Sali A, Stevens RL. Huang C, et al. J Biol Chem. 2000 Jan 7;275(1):351-8. doi: 10.1074/jbc.275.1.351. J Biol Chem. 2000. PMID: 10617625
• Mast cell-restricted tetramer-forming tryptases and their beneficial roles in hemostasis and blood coagulation.
  Prieto-García A, Castells MC, Hansbro PM, Stevens RL. Prieto-García A, et al. Immunol Allergy Clin North Am. 2014 May;34(2):263-81. doi: 10.1016/j.iac.2014.01.001. Epub 2014 Mar 15. Immunol Allergy Clin North Am. 2014. PMID: 24745673 Review.
• Effector cells of anaphylaxis: mast cells and basophils.
  Schwartz LB. Schwartz LB. Novartis Found Symp. 2004;257:65-74; discussion 74-9, 98-100, 276-85. Novartis Found Symp. 2004. PMID: 15025392 Review.

Cited by

• Genetic Regulation of Tryptase Production and Clinical Impact: Hereditary Alpha Tryptasemia, Mastocytosis and Beyond.
  Sprinzl B, Greiner G, Uyanik G, Arock M, Haferlach T, Sperr WR, Valent P, Hoermann G. Sprinzl B, et al. Int J Mol Sci. 2021 Feb 28;22(5):2458. doi: 10.3390/ijms22052458. Int J Mol Sci. 2021. PMID: 33671092 Free PMC article. Review.
• Dengue virus-elicited tryptase induces endothelial permeability and shock.
  Rathore AP, Mantri CK, Aman SA, Syenina A, Ooi J, Jagaraj CJ, Goh CC, Tissera H, Wilder-Smith A, Ng LG, Gubler DJ, St John AL. Rathore AP, et al. J Clin Invest. 2019 Jul 2;129(10):4180-4193. doi: 10.1172/JCI128426. J Clin Invest. 2019. PMID: 31265436 Free PMC article.
• Mast Cell Protease 7 Promotes Angiogenesis by Degradation of Integrin Subunits.
  de Souza Junior DA, Santana C, Vieira GV, Oliver C, Jamur MC. de Souza Junior DA, et al. Cells. 2019 Apr 12;8(4):349. doi: 10.3390/cells8040349. Cells. 2019. PMID: 31013764 Free PMC article.
• Experimental Arthritis Is Dependent on Mouse Mast Cell Protease-5.
  Stevens RL, McNeil HP, Wensing LA, Shin K, Wong GW, Hansbro PM, Krilis SA. Stevens RL, et al. J Biol Chem. 2017 Mar 31;292(13):5392-5404. doi: 10.1074/jbc.M116.773416. Epub 2017 Feb 13. J Biol Chem. 2017. PMID: 28193842 Free PMC article.
• Mast Cell Proteases 6 and 7 Stimulate Angiogenesis by Inducing Endothelial Cells to Release Angiogenic Factors.
  de Souza Junior DA, Borges AC, Santana AC, Oliver C, Jamur MC. de Souza Junior DA, et al. PLoS One. 2015 Dec 3;10(12):e0144081. doi: 10.1371/journal.pone.0144081. eCollection 2015. PLoS One. 2015. PMID: 26633538 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information

• Molecular Biology Databases

  • BioCyc
  • Gene Ontology
  • Mouse Genome Informatics (MGI)