Skip to main content

Hematophagy and Inhibition of the Extrinsic and Intrinsic Tenase Complexes

  • Chapter
  • First Online:
Toxins and Hemostasis

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Andersen, J.F., Gudderra, N.P., Francischetti, I.M., Valenzuela, J.G., Ribeiro, J.M., 2004. Recognition of anionic phospholipid membranes by an antihemostatic protein from a blood-feeding insect. Biochemistry 43, 6987–6994.

    Article  PubMed  CAS  Google Scholar 

  • Andersen, J.F., Montfort, W.R., 2000. The crystal structure of nitrophorin 2. A trifunctional antihemostatic protein from the saliva of Rhodnius prolixus. J. Biol. Chem. 275, 30496–30503.

    Article  PubMed  CAS  Google Scholar 

  • Bauer, K.A., Kass, B.L., ten Cate, H., Hawiger, J.J., Rosenberg, R.D., 1990. Factor IX is activated in vivo by the tissue factor mechanism. Blood 76, 731–736.

    PubMed  CAS  Google Scholar 

  • Baugh, R.J., Broze, G.J., Jr., Krishnaswamy, S., 1998. Regulation of extrinsic pathway factor Xa formation by tissue factor pathway inhibitor. J. Biol. Chem. 273, 4378–4386.

    Article  PubMed  CAS  Google Scholar 

  • Belting, M., Ahamed, J., Ruf, W., 2005. Signaling of the tissue factor coagulation pathway in angiogenesis cancer. Arterioscler. Thromb. Vasc. Biol. 25, 1545–1550.

    Article  PubMed  CAS  Google Scholar 

  • Bergum, P.W., Cruikshank, A., Maki, S.L., Kelly, C.R., Ruf, W., Vlasuk, G.P., 2001. Role of zymogen and activated factor X as scaffolds for the inhibition of the blood coagulation factor VIIa-tissue factor complex by recombinant nematode anticoagulant protein c2. J. Biol. Chem. 276, 10063–10071.

    Article  PubMed  CAS  Google Scholar 

  • Broze, G.J., Jr., 1995. Tissue factor pathway inhibitor and the revised theory of coagulation. Annu. Rev. Med. 46, 103–112.

    Article  PubMed  CAS  Google Scholar 

  • Buddai, S.K., Toulokhonova, L., Bergum, P.W., Vlasuk, G.P., Krishnaswamy, S., 2002. Nematode anticoagulant protein c2 reveals a site on factor Xa that is important for macromolecular substrate binding to human prothrombinase. J. Biol. Chem. 277, 26689–26698.

    Article  PubMed  CAS  Google Scholar 

  • Bunnett, N.W., 2006. Protease-activated receptors: how proteases signal to cells to cause inflammation and pain. Semin. Thromb. Hemost. 32(Suppl 1), 39–48.

    Article  PubMed  CAS  Google Scholar 

  • Camerer, E., Huang, W., Coughlin, S.R., 2000. Tissue factor- and factor X-dependent activation of protease-activated receptor 2 by factor VIIa. Proc. Natl. Acad. Sci. U.S.A. 97, 5255–5260.

    Article  PubMed  CAS  Google Scholar 

  • Carneiro-Lobo, T.C., Konig, S., Machado, D.E., Nasciutti, L.E., Forni, M.F., Francischetti, I.M., Sogayar, M.C., Monteiro, R.Q., 2009. Ixolaris, a tissue factor inhibitor, blocks primary tumor growth and angiogenesis in a glioblastoma model. J. Thromb. Haemost. 7, 1855–1864.

    Google Scholar 

  • Champagne, D.E., Nussenzveig, R.H., Ribeiro, J.M., 1995. Purification, partial characterization, and cloning of nitric oxide-carrying heme proteins (nitrophorins) from salivary glands of the blood-sucking insect Rhodnius prolixus. J. Biol. Chem. 270, 8691–8695.

    Article  PubMed  CAS  Google Scholar 

  • Coughlin, S.R., 2005. Protease-activated receptors in hemostasis, thrombosis and vascular biology. J. Thromb. Haemost. 3, 1800–1814.

    Article  PubMed  CAS  Google Scholar 

  • Davie, E.W., Fujikawa, K., Kisiel, W., 1991. The coagulation cascade: initiation, maintenance, and regulation. Biochemistry 30, 10363–10370.

    Article  PubMed  CAS  Google Scholar 

  • Duggan, B.M., Dyson, H.J., Wright, P.E., 1999. Inherent flexibility in a potent inhibitor of blood coagulation, recombinant nematode anticoagulant protein c2. Eur. J. Biochem. 265, 539–548.

    Article  PubMed  CAS  Google Scholar 

  • Esmon, C.T., 2003. The protein C pathway. Chest 124, 26S–32S.

    Article  PubMed  CAS  Google Scholar 

  • Fluture, A., Giugliano, G.R., Giugliano, R.P., 2007. Recombinant nematode anticoagulant protein c2 in non-ST segment elevation acute coronary syndrome and beyond. Future Cardiol. 3, 365–375.

    Article  PubMed  CAS  Google Scholar 

  • Francischetti, I.M., 2008. Does activation of the blood coagulation cascade have a role in malaria pathogenesis? Trends Parasitol. 24, 258–263.

    Article  PubMed  CAS  Google Scholar 

  • Francischetti, I.M., Mather, T.N., Ribeiro, J.M., 2004. Penthalaris, a novel recombinant five-Kunitz tissue factor pathway inhibitor (TFPI) from the salivary gland of the tick vector of Lyme disease, Ixodes scapularis. Thromb. Haemost. 91, 886–898.

    PubMed  CAS  Google Scholar 

  • Francischetti, I.M., Sa-Nunes, A., Mans, B.J., Santos, I.M., Ribeiro, J.M., 2009. The role of saliva in tick feeding. Front. Biosci. 14, 2051–2088.

    Article  PubMed  CAS  Google Scholar 

  • Francischetti, I.M., Seydel, K.B., Monteiro, R.Q., 2008. Blood coagulation, inflammation, and malaria. Microcirculation 15, 81–107.

    Article  PubMed  CAS  Google Scholar 

  • Francischetti, I.M., Valenzuela, J.G., Andersen, J.F., Mather, T.N., Ribeiro, J.M., 2002. Ixolaris, a novel recombinant tissue factor pathway inhibitor (TFPI) from the salivary gland of the tick, Ixodes scapularis: identification of factor X and factor Xa as scaffolds for the inhibition of factor VIIa/tissue factor complex. Blood 99, 3602–3612.

    Article  PubMed  CAS  Google Scholar 

  • Furie, B., Furie, B.C., 2003. Real time in vivo imaging of tissue factor-induced thrombus formation. Pathophysiol. Haemost. Thromb. 33(Suppl 1), 26–27.

    Article  PubMed  Google Scholar 

  • Gailani, D., Broze, G.J., Jr., 1991. Factor XI activation in a revised model of blood coagulation. Science 253, 909–912.

    Article  PubMed  CAS  Google Scholar 

  • Geisbert, T.W., Hensley, L.E., Jahrling, P.B., Larsen, T., Geisbert, J.B., Paragas, J., Young, H.A., Fredeking, T.M., Rote, W.E., Vlasuk, G.P., 2003. Treatment of Ebola virus infection with a recombinant inhibitor of factor VIIa/tissue factor: a study in rhesus monkeys. Lancet 362, 1953–1958.

    Article  PubMed  CAS  Google Scholar 

  • Giesen, P.L., Rauch, U., Bohrmann, B., Kling, D., Roque, M., Fallon, J.T., Badimon, J.J., Himber, J., Riederer, M.A., Nemerson, Y., 1999. Blood-borne tissue factor: another view of thrombosis. Proc. Natl. Acad. Sci. U.S.A. 96, 2311–2315.

    Article  PubMed  CAS  Google Scholar 

  • Gudderra, N.P., Ribeiro, J.M., Andersen, J.F., 2005. Structural determinants of factor IX(a) binding in nitrophorin 2, a lipocalin inhibitor of the intrinsic coagulation pathway. J. Biol. Chem. 280, 25022–25028.

    Article  PubMed  CAS  Google Scholar 

  • Hembrough, T.A., Swartz, G.M., Papathanassiu, A., Vlasuk, G.P., Rote, W.E., Green, S.J., Pribluda, V.S., 2003. Tissue factor/factor VIIa inhibitors block angiogenesis and tumor growth through a nonhemostatic mechanism. Cancer Res. 63, 2997–3000.

    PubMed  CAS  Google Scholar 

  • Isawa, H., Yuda, M., Yoneda, K., Chinzei, Y., 2000. The insect salivary protein, prolixin-S, inhibits factor IXa generation and Xase complex formation in the blood coagulation pathway. J. Biol. Chem. 275, 6636–6641.

    Article  PubMed  CAS  Google Scholar 

  • Kalafatis, M., Swords, N.A., Rand, M.D., Mann, K.G., 1994. Membrane-dependent reactions in blood coagulation: role of the vitamin K-dependent enzyme complexes. Biochim. Biophys. Acta 1227, 113–129.

    Article  PubMed  Google Scholar 

  • Knipp, M., Yang, F., Berry, R.E., Zhang, H., Shokhirev, M.N., Walker, F.A., 2007a. Spectroscopic and functional characterization of nitrophorin 7 from the blood-feeding insect Rhodnius prolixus reveals an important role of its isoform-specific N-terminus for proper protein function. Biochemistry 46, 13254–13268.

    Article  PubMed  CAS  Google Scholar 

  • Knipp, M., Zhang, H., Berry, R.E., Walker, F.A., 2007b. Overexpression in Escherichia coli and functional reconstitution of the liposome binding ferriheme protein nitrophorin 7 from the bloodsucking bug Rhodnius prolixus. Protein Expr. Purif. 54, 183–191.

    Article  PubMed  CAS  Google Scholar 

  • Koh, C.Y., Kini, R.M., 2009. Molecular diversity of anticoagulants from haematophagous animals. Thromb. Haemost. 102, 437–453.

    PubMed  CAS  Google Scholar 

  • Krishnaswamy, S., 2005. Exosite-driven substrate specificity and function in coagulation. J. Thromb. Haemost. 3, 54–67.

    Article  PubMed  CAS  Google Scholar 

  • Lee, A., Agnelli, G., Buller, H., Ginsberg, J., Heit, J., Rote, W., Vlasuk, G., Costantini, L., Julian, J., Comp, P., van Der Meer, J., Piovella, F., Raskob, G., Gent, M., 2001. Dose-response study of recombinant factor VIIa/tissue factor inhibitor recombinant nematode anticoagulant protein c2 in prevention of postoperative venous thromboembolism in patients undergoing total knee replacement. Circulation 104, 74–78.

    Article  PubMed  CAS  Google Scholar 

  • Levi, M., van der Poll, T., Buller, H.R., 2004. Bidirectional relation between inflammation and coagulation. Circulation 109, 2698–2704.

    Article  PubMed  Google Scholar 

  • Lorand, L., 2005. Factor XIII and the clotting of fibrinogen: from basic research to medicine. J. Thromb. Haemost. 3, 1337–1348.

    Article  PubMed  CAS  Google Scholar 

  • Mahajan, A.L., Tenorio, X., Pepper, M.S., Baetens, D., Montandon, D., Schlaudraff, K.U., Pittet, B., 2006. Progressive tissue injury in burns is reduced by rNAPc2. Burns 32, 957–963.

    Article  PubMed  Google Scholar 

  • Mann, K.G., Butenas, S., Brummel, K., 2003. The dynamics of thrombin formation. Arterioscler. Thromb. Vasc. Biol. 23, 17–25.

    Article  PubMed  CAS  Google Scholar 

  • Marshall, J.C., 2001. Inflammation, coagulopathy, and the pathogenesis of multiple organ dysfunction syndrome. Crit. Care Med. 29, S99–S106.

    Article  PubMed  CAS  Google Scholar 

  • Monroe, D.M., Hoffman, M., Roberts, H.R., 2002. Platelets and thrombin generation. Arterioscler. Thromb. Vasc. Biol. 22, 1381–1389.

    Article  PubMed  CAS  Google Scholar 

  • Monteiro, R.Q., Rezaie, A.R., Bae, J.S., Calvo, E., Andersen, J.F., Francischetti, I.M., 2008. Ixolaris binding to factor X reveals a precursor state of factor Xa heparin-binding exosite. Protein Sci. 17, 146–153.

    Article  PubMed  CAS  Google Scholar 

  • Monteiro, R.Q., Rezaie, A.R., Ribeiro, J.M., Francischetti, I.M., 2005. Ixolaris: a factor Xa heparin-binding exosite inhibitor. Biochem. J. 387, 871–877.

    Article  PubMed  CAS  Google Scholar 

  • Moons, A.H., Peters, R.J., Bijsterveld, N.R., Piek, J.J., Prins, M.H., Vlasuk, G.P., Rote, W.E., Buller, H.R., 2003. Recombinant nematode anticoagulant protein c2, an inhibitor of the tissue factor/factor VIIa complex, in patients undergoing elective coronary angioplasty. J. Am. Coll. Cardiol. 41, 2147–2153.

    Article  PubMed  CAS  Google Scholar 

  • Moons, A.H., Peters, R.J., Cate, H., Bauer, K.A., Vlasuk, G.P., Buller, H.R., Levi, M., 2002. Recombinant nematode anticoagulant protein c2, a novel inhibitor of tissue factor-factor VIIa activity, abrogates endotoxin-induced coagulation in chimpanzees. Thromb. Haemost. 88, 627–631.

    PubMed  CAS  Google Scholar 

  • Murakami, M.T., Rios-Steiner, J., Weaver, S.E., Tulinsky, A., Geiger, J.H., Arni, R.K., 2007. Intermolecular interactions and characterization of the novel factor Xa exosite involved in macromolecular recognition and inhibition: crystal structure of human Gla-domainless factor Xa complexed with the anticoagulant protein NAPc2 from the hematophagous nematode Ancylostoma caninum. J. Mol. Biol. 366, 602–610.

    Article  PubMed  CAS  Google Scholar 

  • Naito, K., Fujikawa, K., 1991. Activation of human blood coagulation factor XI independent of factor XII. Factor XI is activated by thrombin and factor XIa in the presence of negatively charged surfaces. J. Biol. Chem. 266, 7353–7358.

    PubMed  CAS  Google Scholar 

  • Nazareth, R.A., Tomaz, L.S., Ortiz-Costa, S., Atella, G.C., Ribeiro, J.M., Francischetti, I.M., Monteiro, R.Q., 2006. Antithrombotic properties of Ixolaris, a potent inhibitor of the extrinsic pathway of the coagulation cascade. Thromb. Haemost. 96, 7–13.

    PubMed  CAS  Google Scholar 

  • Opal, S.M., Esmon, C.T., 2003. Bench-to-bedside review: functional relationships between coagulation and the innate immune response and their respective roles in the pathogenesis of sepsis. Crit. Care 7, 23–38.

    Article  PubMed  Google Scholar 

  • Osterud, B., Rapaport, S.I., 1977. Activation of factor IX by the reaction product of tissue factor and factor VII: additional pathway for initiating blood coagulation. Proc. Natl. Acad. Sci. U.S.A. 74, 5260–5264.

    Article  PubMed  CAS  Google Scholar 

  • Rak, J., Milsom, C., May, L., Klement, P., Yu, J., 2006. Tissue factor in cancer and angiogenesis: the molecular link between genetic tumor progression, tumor neovascularization, and cancer coagulopathy. Semin. Thromb. Hemost. 32, 54–70.

    Article  PubMed  CAS  Google Scholar 

  • Rao, L.V., Pendurthi, U.R., 2005. Tissue factor-factor VIIa signaling. Arterioscler. Thromb. Vasc. Biol. 25, 47–56.

    PubMed  CAS  Google Scholar 

  • Rezaie, A.R., 2000. Heparin-binding exosite of factor Xa. Trends Cardiovasc. Med. 10, 333–338.

    Article  PubMed  CAS  Google Scholar 

  • Rezaie, A.R., 2002. Insight into the molecular basis of coagulation proteinase specificity by mutagenesis of the serpin antithrombin. Biochemistry 41, 12179–12185.

    Article  PubMed  CAS  Google Scholar 

  • Rezaie, A.R., Yang, L., 2003. Thrombomodulin allosterically modulates the activity of the anticoagulant thrombin. Proc. Natl. Acad. Sci. U.S.A. 100, 12051–12056.

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro, J.M., Francischetti, I.M., 2003. Role of arthropod saliva in blood feeding: sialome and post-sialome perspectives. Annu. Rev. Entomol. 48, 73–88.

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro, J.M., Hazzard, J.M., Nussenzveig, R.H., Champagne, D.E., Walker, F.A., 1993. Reversible binding of nitric oxide by a salivary heme protein from a bloodsucking insect. Science 260, 539–541.

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro, J.M., Schneider, M., Guimaraes, J.A., 1995. Purification and characterization of prolixin S (nitrophorin 2), the salivary anticoagulant of the blood-sucking bug Rhodnius prolixus. Biochem. J. 308(Pt 1), 243–249.

    PubMed  CAS  Google Scholar 

  • Rickles, F.R., Edwards, R.L., 1983. Activation of blood coagulation in cancer: Trousseau’s syndrome revisited. Blood 62, 14–31.

    PubMed  CAS  Google Scholar 

  • Riewald, M., Kravchenko, V.V., Petrovan, R.J., O’Brien, P.J., Brass, L.F., Ulevitch, R.J., Ruf, W., 2001. Gene induction by coagulation factor Xa is mediated by activation of protease-activated receptor 1. Blood 97, 3109–3116.

    Article  PubMed  CAS  Google Scholar 

  • Riewald, M., Ruf, W., 2003. Science review: role of coagulation protease cascades in sepsis. Crit. Care 7, 123–129.

    Article  PubMed  Google Scholar 

  • Rios-Steiner, J.L., Murakami, M.T., Tulinsky, A., Arni, R.K., 2007. Active and exo-site inhibition of human factor Xa: structure of des-Gla factor Xa inhibited by NAP5, a potent nematode anticoagulant protein from Ancylostoma caninum. J. Mol. Biol. 371, 774–786.

    Article  PubMed  CAS  Google Scholar 

  • Roberts, H.R., Hoffman, M., Monroe, D.M., 2006. A cell-based model of thrombin generation. Semin. Thromb. Hemost. 32 Suppl 1, 32–38.

    Article  CAS  Google Scholar 

  • Ruf, W., 2004. Protease-activated receptor signaling in the regulation of inflammation. Crit. Care Med. 32, S287–292.

    Article  PubMed  CAS  Google Scholar 

  • Sanders, N.L., Bajaj, S.P., Zivelin, A., Rapaport, S.I., 1985. Inhibition of tissue factor/factor VIIa activity in plasma requires factor X an additional plasma component. Blood 66, 204–212.

    PubMed  CAS  Google Scholar 

  • Slofstra, S.H., Spek, C.A., ten Cate, H., 2003. Disseminated intravascular coagulation. Hematol. J. 4, 295–302.

    Article  PubMed  Google Scholar 

  • Stassens, P., Bergum, P.W., Gansemans, Y., Jespers, L., Laroche, Y., Huang, S., Maki, S., Messens, J., Lauwereys, M., Cappello, M., Hotez, P.J., Lasters, I., Vlasuk, G.P., 1996. Anticoagulant repertoire of the hookworm Ancylostoma caninum. Proc. Natl. Acad. Sci. U.S.A. 93, 2149–2154.

    Article  PubMed  CAS  Google Scholar 

  • Steinhoff, M., Buddenkotte, J., Shpacovitch, V., Rattenholl, A., Moormann, C., Vergnolle, N., Luger, T.A., Hollenberg, M.D., 2005. Proteinase-activated receptors: transducers of proteinase-mediated signaling in inflammation and immune response. Endocr. Rev. 26, 1–43.

    Article  PubMed  CAS  Google Scholar 

  • Sun, J., Yamaguchi, M., Yuda, M., Miura, K., Takeya, H., Hirai, M., Matsuoka, H., Ando, K., Watanabe, T., Suzuki, K., Chinzei, Y., 1996. Purification, characterization and cDNA cloning of a novel anticoagulant of the intrinsic pathway, (prolixin-S) from salivary glands of the blood sucking bug, Rhodnius prolixus. Thromb. Haemost. 75, 573–577.

    PubMed  CAS  Google Scholar 

  • Taylor, F.B., Jr., Wada, H., Kinasewitz, G., 2000. Description of compensated and uncompensated disseminated intravascular coagulation (DIC) responses (non-overt and overt DIC) in baboon models of intravenous and intraperitoneal Escherichia coli sepsis and in the human model of endotoxemia: toward a better definition of DIC. Crit. Care Med. 28, S12–19.

    Article  PubMed  Google Scholar 

  • ten Cate, H., Bauer, K.A., Levi, M., Edgington, T.S., Sublett, R.D., Barzegar, S., Kass, B.L., Rosenberg, R.D., 1993. The activation of factor X and prothrombin by recombinant factor VIIa in vivo is mediated by tissue factor. J. Clin. Invest. 92, 1207–1212.

    Article  PubMed  Google Scholar 

  • ten Cate, H., Biemond, B.J., Levi, M., Wuillemin, W.A., Bauer, K.A., Barzegar, S., Buller, H.R., Hack, C.E., ten Cate, J.W., Rosenberg, R.D., 1996. Factor XIa induced activation of the intrinsic cascade in vivo. Thromb. Haemost. 75, 445–449.

    PubMed  Google Scholar 

  • Vlasuk, G.P., Bradbury, A., Lopez-Kinninger, L., Colon, S., Bergum, P.W., Maki, S., Rote, W.E., 2003. Pharmacokinetics and anticoagulant properties of the factor VIIa-tissue factor inhibitor recombinant nematode anticoagulant protein c2 following subcutaneous administration in man. Dependence on the stoichiometric binding to circulating factor X. Thromb. Haemost. 90, 803–812.

    PubMed  CAS  Google Scholar 

  • Vlasuk, G.P., Rote, W.E., 2002. Inhibition of factor VIIa/tissue factor with nematode anticoagulant protein c2: from unique mechanism to a promising new clinical anticoagulant. Trends Cardiovasc. Med. 12, 325–331.

    Article  PubMed  CAS  Google Scholar 

  • Vu, T.K., Hung, D.T., Wheaton, V.I., Coughlin, S.R., 1991. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell 64, 1057–1068.

    Article  PubMed  CAS  Google Scholar 

  • Weichsel, A., Andersen, J.F., Champagne, D.E., Walker, F.A., Montfort, W.R., 1998. Crystal structures of a nitric oxide transport protein from a blood-sucking insect. Nat. Struct. Biol. 5, 304–309.

    Article  PubMed  CAS  Google Scholar 

  • Yuda, M., Higuchi, K., Sun, J., Kureishi, Y., Ito, M., Chinzei, Y., 1997. Expression, reconstitution and characterization of prolixin-S as a vasodilator – a salivary gland nitric-oxide-binding hemoprotein of Rhodnius prolixus. Eur. J. Biochem. 249, 337–342.

    Article  PubMed  CAS  Google Scholar 

  • Zacharski, L.R., 2002. Anticoagulants in cancer treatment: malignancy as a solid phase coagulopathy. Cancer Lett. 186, 1–9.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, Y., Ribeiro, J.M., Guimaraes, J.A., Walsh, P.N., 1998. Nitrophorin-2: a novel mixed-type reversible specific inhibitor of the intrinsic factor-X activating complex. Biochemistry 37, 10681–10690.

    Article  PubMed  CAS  Google Scholar 

  • Zhao, J., Aguilar, G., Palencia, S., Newton, E., Abo, A., 2009. rNAPc2 inhibits colorectal cancer in mice through tissue factor. Clin. Cancer Res. 15, 208–216.

    Article  PubMed  CAS  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Robson Q. Monteiro .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Monteiro, R.Q., Andersen, J.F., Francischetti, I.M. (2010). Hematophagy and Inhibition of the Extrinsic and Intrinsic Tenase Complexes. In: Kini, R., Clemetson, K., Markland, F., McLane, M., Morita, T. (eds) Toxins and Hemostasis. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9295-3_14

Download citation

Publish with us

Policies and ethics