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Hematophagy and Inhibition of the Extrinsic and Intrinsic Tenase Complexes

  • Robson Q. Monteiro
  • John F. Andersen
  • Ivo M.B. Francischetti
Chapter

Abstract

The coagulation cascade involves the regulated sequence of proteolytic activation of a series of zymogens culminating in conversion of fibrinogen to fibrin and clot formation. These reactions are mainly performed by enzymatic complexes comprised of a serine protease, a protein cofactor and membranes containing anionic phospholipids. A number of specific coagulation inhibitors from exogenous sources have been identified from salivary glands of blood-sucking arthropods and herein named sialogenins (from the Greek sialo, saliva; gen, origin, source; and ins for proteins) with anticlotting activity.

Anti-clotting sialogenins target components of the extrinsic (e.g. ixolaris, penthalaris, NAPc2) or intrinsic Xase (e.g. nitrophorin 2, nitrophorin 7) complexes resulting in inhibition of the initiation, propagation or consolidation steps of blood coagulation cascade. In addition, these molecules act in a redundant and synergistic manner in order to keep hemostatic tonus as low as possible so as to facilitate blood-feeding. These molecules may also attenuate inflammatory events associated with vascular injury. Finally, anti-clotting sialogenins have potential therapeutic applications and are valuable tools in pharmacology and cell biology.

Keywords

Tissue Factor Coagulation Cascade Tissue Factor Expression Primary Tumor Growth Coagulation Inhibitor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. We thank NIAID intramural editor Brenda Rae Marshall for assistance.

Because J.F.A. and I.M.B.F. are government employees and this is a government work, the work is in the public domain in the United States. Notwithstanding any other agreements, the NIH reserves the right to provide the work to PubMedCentral for display and use by the public, and PubMedCentral may tag or modify the work consistent with its customary practices. You can establish rights outside of the U.S. subject to a government use license.

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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Robson Q. Monteiro
    • 1
  • John F. Andersen
    • 2
  • Ivo M.B. Francischetti
    • 2
  1. 1.Instituto de Bioquímica MédicaUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil
  2. 2.Section of Vector Biology, Laboratory of Malaria and Vector ResearchNational Institute of Allergy and Infectious Diseases, National Institutes of HealthRockvilleUSA

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