Advertisement

Hematophagy and Inhibition of Platelet Aggregation

  • Ivo M.B. FrancischettiEmail author
Chapter

Abstract

Salivary glands from blood-sucking animals (e.g., mosquitoes, bugs, sandflies, fleas, ticks, leeches, hookworms, bats) are a rich source of bioactive molecules that counteract hemostasis in a redundant and synergistic manner. This review discusses recent progress in the identification of salivary inhibitors of platelet aggregation, their molecular characterization, and detailed mechanism of action. Diversity of inhibitors is remarkable, with distinct families of proteins characterized as apyrases that enzymatically degrade ADP or as collagen-binding proteins that prevent its interaction with vWF, or platelet integrin a2b1 or GPVI. Molecules that bind ADP, TXA2, epinephrine, or serotonin with high affinity have also been cloned, expressed, and their structure determined. In addition, a repertoire of antithrombins and an increasingly number of RGD and non-RGD disintegrins targeting platelet aIIbb3 have been reported. Moreover, metalloproteases with fibrinogen (olytic) activity and PAF phosphorylcholine hydrolase are enzymes that have been recruited to the salivary gland to block platelet aggregation. Platelet inhibitory prostaglandins, lysophosphatydilcholine, adenosine, and nitric oxide (NO)-carrying proteins are other notable examples of molecules from hematophagous salivary secretions (herein named sialogenins) with antihemostatic properties. Sialogenins have been employed as tools in biochemistry and cell biology and also display potential therapeutic applications.

Keywords

Aegyptin Ixolaris D7-short RPAI-1 Nitrophorin Anophelin Lipocalin Tick Mosquito Sand fly Ixodegrin Ornatin Metalloproteases Sialogenin 

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 I am a government employee 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.

References

  1. Aljamali, M., Bowman, A.S., Dillwith, J.W., Tucker, J.S., Yates, G.W., Essenberg, R.C., Sauer, J.R., 2002. Identity and synthesis of prostaglandins in the lone star tick, Amblyomma americanum (L.), as assessed by radio-immunoassay and gas chromatography/mass spectrometry. Insect Biochem. Mol. Biol. 32, 331–341.PubMedCrossRefGoogle Scholar
  2. Andersen, J.F., Francischetti, I.M., Valenzuela, J.G., Schuck, P., Ribeiro, J.M., 2003. Inhibition of hemostasis by a high affinity biogenic amine-binding protein from the saliva of a blood-feeding insect. J. Biol. Chem. 278, 4611–4617.PubMedCrossRefGoogle Scholar
  3. 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.PubMedCrossRefGoogle Scholar
  4. Andersen, J.F., Hinnebusch, B.J., Lucas, D.A., Conrads, T.P., Veenstra, T.D., Pham, V.M., Ribeiro, J.M., 2007. An insight into the sialome of the oriental rat flea, Xenopsylla cheopis (Rots). BMC Genomics 8, 102.PubMedCrossRefGoogle Scholar
  5. Barnes, C.S., Krafft, B., Frech, M., Hofmann, U.R., Papendieck, A., Dahlems, U., Gellissen, G., Hoylaerts, M.F., 2001. Production and characterization of saratin, an inhibitor of von Willebrand factor-dependent platelet adhesion to collagen. Semin. Thromb. Hemost. 27, 337–348.PubMedCrossRefGoogle Scholar
  6. Budzynski, A.Z., 1991. Interaction of hementin with fibrinogen and fibrin. Blood Coagul. Fibrinolysis 2, 149–152.PubMedCrossRefGoogle Scholar
  7. Calvo, E., Mans, B.J., Andersen, J.F., Ribeiro, J.M., 2006. Function and evolution of a mosquito salivary protein family. J. Biol. Chem. 281, 1935–1942.PubMedCrossRefGoogle Scholar
  8. Calvo, E., Mans, B.J., Ribeiro, J.M., Andersen, J.F., 2009. Multifunctionality and mechanism of ligand binding in a mosquito antiinflammatory protein. Proc. Natl. Acad. Sci. U.S.A. 106, 3728–3733.PubMedCrossRefGoogle Scholar
  9. Calvo, E., Tokumasu, F., Marinotti, O., Villeval, J.L., Ribeiro, J.M., Francischetti, I.M., 2007. Aegyptin, a novel mosquito salivary gland protein, specifically binds to collagen and prevents its interaction with platelet glycoprotein VI, integrin α2β1, and von Willebrand factor. J. Biol. Chem. 282, 26928–26938.PubMedCrossRefGoogle Scholar
  10. Calvo, E., Tokumasu, F., Mizurini, D.M., McPhie, P., Narum, D.L., Ribeiro, J.M., Monteiro, R.Q., Francischetti, I.M., 2010. Aegyptin displays high-affinity for the von Willebrand factor binding site (RGQOGVMGF) in collagen and inhibits carotid thrombus formation in vivo. FEBS J. 277(2), 413–427.PubMedCrossRefGoogle Scholar
  11. Champagne, D.E., Smartt, C.T., Ribeiro, J.M., James, A.A., 1995. The salivary gland-specific apyrase of the mosquito Aedes aegypti is a member of the 5'-nucleotidase family. Proc. Natl. Acad. Sci. U.S.A. 92, 694–698.PubMedCrossRefGoogle Scholar
  12. Charlab, R., Valenzuela, J.G., Rowton, E.D., Ribeiro, J.M., 1999. Toward an understanding of the biochemical and pharmacological complexity of the saliva of a hematophagous sand fly Lutzomyia longipalpis. Proc. Natl. Acad. Sci. U.S.A. 96, 15155–15160.PubMedCrossRefGoogle Scholar
  13. Cheng, Y., Wu, H., Li, D., 1999. An inhibitor selective for collagen-stimulated platelet aggregation from the salivary glands of hard tick Haemaphysalis longicornis and its mechanism of action. Sci. China C. Life Sci. 42, 457–464.PubMedCrossRefGoogle Scholar
  14. Chudzinski-Tavassi, A.M., Kelen, E.M., de Paula Rosa, A.P., Loyau, S., Sampaio, C.A., Bon, C., Angles-Cano, E., 1998. Fibrino(geno)lytic properties of purified hementerin, a metalloproteinase from the leech Haementeria depressa. Thromb. Haemost. 80, 155–160.PubMedGoogle Scholar
  15. Connolly, T.M., Jacobs, J.W., Condra, C., 1992. An inhibitor of collagen-stimulated platelet activation from the salivary glands of the Haementeria officinalis leech. I. Identification, isolation, and characterization. J. Biol. Chem. 267, 6893–6898.PubMedGoogle Scholar
  16. Coughlin, S.R., 2005. Protease-activated receptors in hemostasis, thrombosis and vascular biology. J. Thromb. Haemost. 3, 1800–1814.PubMedCrossRefGoogle Scholar
  17. Cruz, C.P., Eidt, J., Drouilhet, J., Brown, A.T., Wang, Y., Barnes, C.S., Moursi, M.M., 2001. Saratin, an inhibitor of von Willebrand factor-dependent platelet adhesion, decreases platelet aggregation and intimal hyperplasia in a rat carotid endarterectomy model. J. Vasc. Surg. 34, 724–729.PubMedCrossRefGoogle Scholar
  18. Dai, J., Liu, J., Deng, Y., Smith, T.M., Lu, M., 2004. Structure and protein design of a human platelet function inhibitor. Cell 116, 649–659.PubMedCrossRefGoogle Scholar
  19. Deckmyn, H., Stassen, J.M., Vreys, I., Van Houtte, E., Sawyer, R.T., Vermylen, J., 1995. Calin from Hirudo medicinalis, an inhibitor of platelet adhesion to collagen, prevents platelet-rich thrombosis in hamsters. Blood 85, 712–719.PubMedGoogle Scholar
  20. Del Valle, A., Jones, B.F., Harrison, L.M., Chadderdon, R.C., Cappello, M., 2003. Isolation and molecular cloning of a secreted hookworm platelet inhibitor from adult Ancylostoma caninum. Mol. Biochem. Parasitol. 129, 167–177.PubMedCrossRefGoogle Scholar
  21. Depraetere, H., Kerekes, A., Deckmyn, H., 1999. The collagen-binding leech products rLAPP and calin prevent both von Willebrand factor and α2β1(GPIa/IIa)-I-domain binding to collagen in a different manner. Thromb. Haemost. 82, 1160–1163.PubMedGoogle Scholar
  22. Faudry, E., Lozzi, S.P., Santana, J.M., D‘Souza-Ault, M., Kieffer, S., Felix, C.R., Ricart, C.A., Sousa, M.V., Vernet, T., Teixeira, A.R., 2004. Triatoma infestans apyrases belong to the 5'-nucleotidase family. J. Biol. Chem. 279, 19607–19613.PubMedCrossRefGoogle Scholar
  23. Francischetti, I.M., Andersen, J.F., Ribeiro, J.M., 2002. Biochemical and functional characterization of recombinant Rhodnius prolixus platelet aggregation inhibitor 1 as a novel lipocalin with high affinity for adenosine diphosphate and other adenine nucleotides. Biochemistry 41, 3810–3818.PubMedCrossRefGoogle Scholar
  24. Francischetti, I.M., Mather, T.N., Ribeiro, J.M., 2003. Cloning of a salivary gland metalloprotease and characterization of gelatinase and fibrin(ogen)lytic activities in the saliva of the Lyme disease tick vector Ixodes scapularis. Biochem. Biophys. Res. Commun. 305, 869–875.PubMedCrossRefGoogle Scholar
  25. Francischetti, I.M., Meng, Z., Mans, B.J., Gudderra, N., Hall, M., Veenstra, T.D., Pham, V.M., Kotsyfakis, M., Ribeiro, J.M., 2008. An insight into the salivary transcriptome and proteome of the soft tick and vector of epizootic bovine abortion, Ornithodoros coriaceus. J. Proteomics 71, 493–512.PubMedCrossRefGoogle Scholar
  26. Francischetti, I.M., My Pham, V., Mans, B.J., Andersen, J.F., Mather, T.N., Lane, R.S., Ribeiro, J.M., 2005. The transcriptome of the salivary glands of the female western black-legged tick Ixodes pacificus (Acari: Ixodidae). Insect Biochem. Mol. Biol. 35, 1142–1161.PubMedCrossRefGoogle Scholar
  27. Francischetti, I.M., Ribeiro, J.M., Champagne, D., Andersen, J., 2000. Purification, cloning, expression, and mechanism of action of a novel platelet aggregation inhibitor from the salivary gland of the blood-sucking bug, Rhodnius prolixus. J. Biol. Chem. 275, 12639–12650.PubMedCrossRefGoogle Scholar
  28. 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.PubMedCrossRefGoogle Scholar
  29. Furie, B., Furie, B.C., 2005. Thrombus formation in vivo. J. Clin. Invest. 115, 3355–3362.PubMedCrossRefGoogle Scholar
  30. Gawaz, M., Langer, H., May, A.E., 2005. Platelets in inflammation and atherogenesis. J. Clin. Invest. 115, 3378–3384.PubMedCrossRefGoogle Scholar
  31. Golodne, D.M., Monteiro, R.Q., Graca-Souza, A.V., Silva-Neto, M.A., Atella, G.C., 2003. Lysophosphatidylcholine acts as an anti-hemostatic molecule in the saliva of the blood-sucking bug Rhodnius prolixus. J. Biol. Chem. 278, 27766–27771.PubMedCrossRefGoogle Scholar
  32. Gronwald, W., Bomke, J., Maurer, T., Domogalla, B., Huber, F., Schumann, F., Kremer, W., Fink, F., Rysiok, T., Frech, M., Kalbitzer, H.R., 2008. Structure of the leech protein saratin and characterization of its binding to collagen. J. Mol. Biol. 381, 913–927.PubMedCrossRefGoogle Scholar
  33. Gross, P.L., Weitz, J.I., 2009. New antithrombotic drugs. Clin. Pharmacol. Ther. 86, 139–146.PubMedCrossRefGoogle Scholar
  34. Harsfalvi, J., Stassen, J.M., Hoylaerts, M.F., Van Houtte, E., Sawyer, R.T., Vermylen, J., Deckmyn, H., 1995. Calin from Hirudo medicinalis, an inhibitor of von Willebrand factor binding to collagen under static and flow conditions. Blood 85, 705–711.PubMedGoogle Scholar
  35. Huizinga, E.G., Schouten, A., Connolly, T.M., Kroon, J., Sixma, J.J., Gros, P., 2001. The structure of leech anti-platelet protein, an inhibitor of haemostasis. Acta Crystallogr. D. Biol. Crystallogr. 57, 1071–1078.PubMedCrossRefGoogle Scholar
  36. Jackson, S.P., Schoenwaelder, S.M., 2003. Antiplatelet therapy: in search of the ‘magic bullet‘. Nat Rev. Drug Discov. 2, 775–789.PubMedCrossRefGoogle Scholar
  37. Jandrot-Perrus, M., Busfield, S., Lagrue, A.H., Xiong, X., Debili, N., Chickering, T., Le Couedic, J.P., Goodearl, A., Dussault, B., Fraser, C., Vainchenker, W., Villeval, J.L., 2000. Cloning, characterization, and functional studies of human and mouse glycoprotein VI: a platelet-specific collagen receptor from the immunoglobulin superfamily. Blood 96, 1798–1807.PubMedGoogle Scholar
  38. Jones, R.L., Giembycz, M.A., Woodward, D.F., 2009. Prostanoid receptor antagonists: development strategies and therapeutic applications. Br. J. Pharmacol. 158, 104–145.PubMedCrossRefGoogle Scholar
  39. Kahner, B.N., Shankar, H., Murugappan, S., Prasad, G.L., Kunapuli, S.P., 2006. Nucleotide receptor signaling in platelets. J. Thromb. Haemost. 4, 2317–2326.PubMedCrossRefGoogle Scholar
  40. Karczewski, J., Endris, R., Connolly, T.M., 1994. Disagregin is a fibrinogen receptor antagonist lacking the Arg-Gly-Asp sequence from the tick, Ornithodoros moubata. J. Biol. Chem. 269, 6702–6708.PubMedGoogle Scholar
  41. Karczewski, J., Waxman, L., Endris, R.G., Connolly, T.M., 1995. An inhibitor from the argasid tick Ornithodoros moubata of cell adhesion to collagen. Biochem. Biophys. Res. Commun. 208, 532–541.PubMedCrossRefGoogle Scholar
  42. Keller, P.M., Schultz, L.D., Condra, C., Karczewski, J., Connolly, T.M., 1992. An inhibitor of collagen-stimulated platelet activation from the salivary glands of the Haementeria officinalis leech. II. Cloning of the cDNA and expression. J. Biol. Chem. 267, 6899–6904.PubMedGoogle Scholar
  43. Keller, P.M., Waxman, L., Arnold, B.A., Schultz, L.D., Condra, C., Connolly, T.M., 1993. Cloning of the cDNA and expression of moubatin, an inhibitor of platelet aggregation. J. Biol. Chem. 268, 5450–5456.PubMedGoogle Scholar
  44. Koh, C.Y., Kini, R.M., 2009. Molecular diversity of anticoagulants from haematophagous animals. Thromb. Haemost. 102, 437–453.PubMedGoogle Scholar
  45. Krezel, A.M., Wagner, G., Seymour-Ulmer, J., Lazarus, R.A., 1994. Structure of the RGD protein decorsin: conserved motif and distinct function in leech proteins that affect blood clotting. Science 264, 1944–1947.PubMedCrossRefGoogle Scholar
  46. Liyou, N., Hamilton, S., Elvin, C., Willadsen, P., 1999. Cloning and expression of ecto 5-nucleotidase from the cattle tick Boophilus microplus. Insect Mol. Biol. 8, 257–266.PubMedCrossRefGoogle Scholar
  47. Lombardo, F., Di Cristina, M., Spanos, L., Louis, C., Coluzzi, M., Arca, B., 2000. Promoter sequences of the putative Anopheles gambiae apyrase confer salivary gland expression in Drosophila melanogaster. J. Biol. Chem. 275, 23861–23868.PubMedCrossRefGoogle Scholar
  48. Lu, Q., Clemetson, J.M., Clemetson, K.J., 2005. Snake venoms and hemostasis. J. Thromb. Haemost. 3, 1791–1799.PubMedCrossRefGoogle Scholar
  49. Ma, D., Wang, Y., Yang, H., Wu, J., An, S., Gao, L., Xu, X., Lai, R., 2009. Anti-thrombosis repertoire of blood-feeding horsefly salivary glands. Mol. Cell. Proteomics 8, 2071–2079.PubMedCrossRefGoogle Scholar
  50. Mans, B.J., Andersen, J.F., Schwan, T.G., Ribeiro, J.M., 2008a. Characterization of anti-hemostatic factors in the argasid, Argas monolakensis: implications for the evolution of blood-feeding in the soft tick family. Insect Biochem. Mol. Biol. 38, 22–41.PubMedCrossRefGoogle Scholar
  51. Mans, B.J., Louw, A.I., Neitz, A.W., 2002. Savignygrin, a platelet aggregation inhibitor from the soft tick Ornithodoros savignyi, presents the RGD integrin recognition motif on the Kunitz-BPTI fold. J. Biol. Chem. 277, 21371–21378.PubMedCrossRefGoogle Scholar
  52. Mans, B.J., Ribeiro, J.M., 2008. Function, mechanism and evolution of the moubatin-clade of soft tick lipocalins. Insect Biochem. Mol. Biol. 38, 841–852.PubMedCrossRefGoogle Scholar
  53. Mans, B.J., Ribeiro, J.M., Andersen, J.F., 2008b. Structure, function, and evolution of biogenic amine-binding proteins in soft ticks. J. Biol. Chem. 283, 18721–18733.PubMedCrossRefGoogle Scholar
  54. Maritz-Olivier, C., Stutzer, C., Jongejan, F., Neitz, A.W., Gaspar, A.R., 2007. Tick anti-hemostatics: targets for future vaccines and therapeutics. Trends Parasitol. 23, 397–407.PubMedCrossRefGoogle Scholar
  55. Mazur, P., Henzel, W.J., Seymour, J.L., Lazarus, R.A., 1991. Ornatins: potent glycoprotein IIb-IIIa antagonists and platelet aggregation inhibitors from the leech Placobdella ornata. Eur. J. Biochem. 202, 1073–1082.PubMedCrossRefGoogle Scholar
  56. McLane, M.A., Gabbeta, J., Rao, A.K., Beviglia, L., Lazarus, R.A., Niewiarowski, S., 1995. A comparison of the effect of decorsin and two disintegrins, albolabrin and eristostatin, on platelet function. Thromb. Haemost. 74, 1316–1322.PubMedGoogle Scholar
  57. Montfort, W.R., Weichsel, A., Andersen, J.F., 2000. Nitrophorins and related antihemostatic lipocalins from Rhodnius prolixus and other blood-sucking arthropods. Biochim. Biophys. Acta 1482, 110–118.PubMedCrossRefGoogle Scholar
  58. Morita, A., Isawa, H., Orito, Y., Iwanaga, S., Chinzei, Y., Yuda, M., 2006. Identification and characterization of a collagen-induced platelet aggregation inhibitor, triplatin, from salivary glands of the assassin bug, Triatoma infestans. FEBS J. 273, 2955–2962.PubMedCrossRefGoogle Scholar
  59. Noeske-Jungblut, C., Kratzschmar, J., Haendler, B., Alagon, A., Possani, L., Verhallen, P., Donner, P., Schleuning, W.D., 1994. An inhibitor of collagen-induced platelet aggregation from the saliva of Triatoma pallidipennis. J. Biol. Chem. 269, 5050–5053.PubMedGoogle Scholar
  60. Reddy, V.B., Kounga, K., Mariano, F., Lerner, E.A., 2000. Chrysoptin is a potent glycoprotein IIb/IIIa fibrinogen receptor antagonist present in salivary gland extracts of the deerfly. J. Biol. Chem. 275, 15861–15867.PubMedCrossRefGoogle Scholar
  61. Ribeiro, J.M., Francischetti, I.M., 2001. Platelet-activating-factor-hydrolyzing phospholipase C in the salivary glands and saliva of the mosquito Culex quinquefasciatus. J. Exp. Biol. 204, 3887–3894.PubMedGoogle Scholar
  62. 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.PubMedCrossRefGoogle Scholar
  63. Ribeiro, J.M., Katz, O., Pannell, L.K., Waitumbi, J., Warburg, A., 1999. Salivary glands of the sand fly Phlebotomus papatasi contain pharmacologically active amounts of adenosine and 5'-AMP. J. Exp. Biol. 202, 1551–1559.PubMedGoogle Scholar
  64. Ribeiro, J.M., Makoul, G.T., Robinson, D.R., 1988. Ixodes dammini: evidence for salivary prostacyclin secretion. J. Parasitol. 74, 1068–1069.PubMedCrossRefGoogle Scholar
  65. Ruggeri, Z.M., 2002. Platelets in atherothrombosis. Nat. Med. 8, 1227–1234.PubMedCrossRefGoogle Scholar
  66. Sangamnatdej, S., Paesen, G.C., Slovak, M., Nuttall, P.A., 2002. A high affinity serotonin- and histamine-binding lipocalin from tick saliva. Insect Mol. Biol. 11, 79–86.PubMedCrossRefGoogle Scholar
  67. Schaffer, L.W., Davidson, J.T., Siegl, P.K., Gould, R.J., Nutt, R.F., Brady, S.F., Connolly, T.M., 1993. Recombinant leech antiplatelet protein prevents collagen-mediated platelet aggregation but not collagen graft thrombosis in baboons. Arterioscler. Thromb. 13, 1593–1601.PubMedCrossRefGoogle Scholar
  68. Seymour, J.L., Henzel, W.J., Nevins, B., Stults, J.T., Lazarus, R.A., 1990. Decorsin. A potent glycoprotein IIb-IIIa antagonist and platelet aggregation inhibitor from the leech Macrobdella decora. J. Biol. Chem. 265, 10143–10147.PubMedGoogle Scholar
  69. Steen, N.A., Barker, S.C., Alewood, P.F., 2006. Proteins in the saliva of the Ixodida (ticks): pharmacological features and biological significance. Toxicon 47, 1–20.PubMedCrossRefGoogle Scholar
  70. Stutzer, C., Mans, B.J., Gaspar, A.R., Neitz, A.W., Maritz-Olivier, C., 2009. Ornithodoros savignyi: soft tick apyrase belongs to the 5'-nucleotidase family. Exp. Parasitol. 122, 318–327.PubMedCrossRefGoogle Scholar
  71. Valenzuela, J.G., Belkaid, Y., Rowton, E., Ribeiro, J.M., 2001. The salivary apyrase of the blood-sucking sand fly Phlebotomus papatasi belongs to the novel Cimex family of apyrases. J. Exp. Biol. 204, 229–237.PubMedGoogle Scholar
  72. Valenzuela, J.G., Charlab, R., Galperin, M.Y., Ribeiro, J.M., 1998. Purification, cloning, and expression of an apyrase from the bed bug Cimex lectularius. A new type of nucleotide-binding enzyme. J. Biol. Chem. 273, 30583–30590.PubMedCrossRefGoogle Scholar
  73. Valenzuela, J.G., Walker, F.A., Ribeiro, J.M., 1995. A salivary nitrophorin (nitric-oxide-carrying hemoprotein) in the bedbug Cimex lectularius. J. Exp. Biol. 198, 1519–1526.PubMedGoogle Scholar
  74. van Zanten, G.H., Connolly, T.M., Schiphorst, M.E., de Graaf, S., Slootweg, P.J., Sixma, J.J., 1995. Recombinant leech antiplatelet protein specifically blocks platelet deposition on collagen surfaces under flow conditions. Arterioscler. Thromb. Vasc. Biol. 15, 1424–1431.PubMedCrossRefGoogle Scholar
  75. Varga-Szabo, D., Pleines, I., Nieswandt, B., 2008. Cell adhesion mechanisms in platelets. Arterioscler. Thromb. Vasc. Biol. 28, 403–412.PubMedCrossRefGoogle Scholar
  76. Vilahur, G., Duran, X., Juan-Babot, O., Casani, L., Badimon, L., 2004. Antithrombotic effects of saratin on human atherosclerotic plaques. Thromb. Haemost. 92, 191–200.PubMedGoogle Scholar
  77. Wang, X., Coons, L.B., Taylor, D.B., Stevens, S.E., Jr., Gartner, T.K., 1996. Variabilin, a novel RGD-containing antagonist of glycoprotein IIb-IIIa and platelet aggregation inhibitor from the hard tick Dermacentor variabilis. J. Biol. Chem. 271, 17785–17790.PubMedCrossRefGoogle Scholar
  78. Watson, S.P., Auger, J.M., McCarty, O.J., Pearce, A.C., 2005. GPVI and integrin αIIbβ3 signaling in platelets. J. Thromb. Haemost. 3, 1752–1762.PubMedCrossRefGoogle Scholar
  79. Waxman, L., Connolly, T.M., 1993. Isolation of an inhibitor selective for collagen-stimulated platelet aggregation from the soft tick Ornithodoros moubata. J. Biol. Chem. 268, 5445–5449.PubMedGoogle Scholar
  80. White, T.C., Berny, M.A., Robinson, D.K., Yin, H., DeGrado, W.F., Hanson, S.R., McCarty, O.J., 2007. The leech product saratin is a potent inhibitor of platelet integrin α2β1 and von Willebrand factor binding to collagen. FEBS J. 274, 1481–1491.PubMedCrossRefGoogle Scholar
  81. Yoshida, S., Sudo, T., Niimi, M., Tao, L., Sun, B., Kambayashi, J., Watanabe, H., Luo, E., Matsuoka, H., 2008. Inhibition of collagen-induced platelet aggregation by anopheline antiplatelet protein, a saliva protein from a malaria vector mosquito. Blood 111, 2007–2014.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Section of Vector Biology, Laboratory of Malaria and Vector ResearchNational Institute of Allergy and Infectious Diseases, National Institutes of HealthRockvilleUSA

Personalised recommendations