Skip to main content
Log in

Disaggregation of Aggregated Platelets by Savignygrin, a αIIbβ3 Antagonist from Ornithodoros Savignyi

  • Published:
Experimental & Applied Acarology Aims and scope Submit manuscript

Abstract

Ticks control their host's hemostatic system by secretion of bioactive components during feeding that inhibit blood coagulation and platelet aggregation. Dissolution of platelets that have already aggregated can enhance control over the hemostatic system. It has been shown that disaggregation of aggregated platelets by the enzyme apyrase was accompanied by a shape change from the aggregated spherical form back to the discoid form associated with un-activated platelets. The present study concerns the disaggregation effect of the αIIbβ3 antagonist, savignygrin. Aggregated platelets that were disaggregated by savignygrin and platelets pre-incubated with savignygrin before activation with ADP, retained a spherical form similar to platelets disaggregated by the fibrinogenolytic enzyme plasmin. The number of pseudopods were however, markedly reduced suggesting a disruption of the focal adhesion points that act as a localization point of αIIbβ3. These results are concurrent with targeting of αIIbβ3 and dissociation of fibrinogen from its receptor, once aggregation has taken place. This is the second mediator of platelet disaggregation found in soft ticks and suggests that disaggregation of aggregated platelets might play an important part in the anti-hemostatic strategy of ticks.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Bowman, A.S., Coons, L.B., Needham, G.R. and Sauer, J.R. 1997. Tick saliva: recent advances and implications for vector competence. Med. Vet. Entomol. 11: 277-285.

    PubMed  CAS  Google Scholar 

  • Calvete, J.J. 1994. Clues for understanding the structure and function of a prototypic human integrin: the platelet glycoprotein IIb/IIIa complex. Thromb. Haemostasis 72: 1-15.

    CAS  Google Scholar 

  • Calvete, J.J. 1995. On the structure and function of platelet integrin αIIbβ3, the fibrinogen receptor. P. Soc. Exp. Biol. Med. 208: 346-360.

    CAS  Google Scholar 

  • de Castro, J.J. and Newson, R.M. 1993. Host resistance in cattle tick control. Parasitol. Today 9: 13-17.

    Article  PubMed  CAS  Google Scholar 

  • Hawiger, J. 1992. Repertoire of platelet receptors. Method Enzymol. 215: 131-136.

    CAS  Google Scholar 

  • Isenberg, W.M., Bainton, D.F. and Newman, P.J. 1990. Monoclonal antibodies bound to subunits of the integrin GPIIb-IIIa are internalized and interfere with filopodia formation and platelet aggregation. Blood 76: 1564-1571.

    PubMed  CAS  Google Scholar 

  • Jamaluddin, M. 1991. New perspectives in blood platelet aggregation. Curr. Sci. 61: 256-533.

    Google Scholar 

  • Karczewski, J., Endris, R. and 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.

    PubMed  CAS  Google Scholar 

  • Kouns, W.C., Fox, C.F., Lamoreaux, W.J., Coons, L.B. and Jennings, L.K. 1991. The effect of glycoprotein IIb-IIIa receptor occupancy on the cytoskeleton of resting and activated platelets. J. Biol. Chem. 266: 13891-13900.

    PubMed  CAS  Google Scholar 

  • Law, J.H., Ribeiro, J.M.C. and Wells, M.A. 1992. Biochemical insights derived from insect diversity. Ann. Rev. Biochem. 64: 87-111.

    Article  Google Scholar 

  • Lehmann, T. 1993. Ectoparasites: direct impact on host fitness. Parasitol. Today. 9: 8-13.

    Article  PubMed  CAS  Google Scholar 

  • Mahlaku, M.M., Gaspar, A.R.M.D. and Neitz, A.W.H. 2001. Characterization of the proteolytic activity present in the salivary glands of the tick, Ornithodoros savignyi. In: IUBMB/SASBMB Special Meeting on: The Biochemical and Molecular Basis of Disease, Cape Town, South Africa, 19-23 November 2001, p230.

  • Mans, B.J., Louw, A.I., Gaspar, A.R.M.D. and Neitz, A.W.H. 1998a. Apyrase activity and platelet aggregation inhibitors in the tick Ornithodoros savignyi. Exp. Appl. Acarol. 22: 353-366.

    Article  PubMed  CAS  Google Scholar 

  • Mans, B.J., Louw, A.I., Gaspar, A.R.M.D. and Neitz, A.W.H. 1998b. Purification and characterization of apyrase from the tick, Ornithodoros savignyi. Comp. Biochem. Phys. B 120: 617-624.

    Article  CAS  Google Scholar 

  • Mans, B.J., Coetzee, J., Louw, A.I., Gaspar, A.R.M.D. and Neitz, A.W.H. 2000. Disaggregation of aggregated platelets by apyrase from the tick, Ornithodoros savignyi (Acari: Argasidae). Exp. Appl. Acarol. 24: 271-282.

    Article  PubMed  CAS  Google Scholar 

  • Mans, B.J., Louw, A.I. and Neitz, A.W.H. 2002a. Amino acid sequence and structure modeling of savignin, a thrombin inhibitor from the tick, Ornithodoros savignyi. Insect Biochem. Molec. 32: 821-828.

    Article  CAS  Google Scholar 

  • Mans, B.J., Louw, A.I. and Neitz, A.W.H. 2002b. 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.

    Article  PubMed  CAS  Google Scholar 

  • Nienaber, J., Gaspar, A.R.M.D. and Neitz, A.W.H. 1999. Savignin, a potent thrombin inhibitor isolated from the salivary glands of the tick, Ornithodoros savignyi (Acari: Argasidae). Exp. Parasitol. 93: 82-91.

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro, J.M.C., Makoul, G., Levine, J., Robinson, D. and Spielman, A. 1985. Antihemostatic, autoinflammatory and immunosuppressive properties of the saliva of a tick Ixodes dammini. J. Exp. Med. 161: 332-344.

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro, J.M.C., Endris, T.M. and Endris, R. 1991. Saliva of the soft tick Ornithodoros moubata contains anti-platelet and apyrase activity. Comp. Biochem. Phys. 100A: 109-112.

    Article  CAS  Google Scholar 

  • Siess, W. 1989. Molecular mechanisms of platelet activation. Physiol. Rev. 69: 58-178.

    PubMed  CAS  Google Scholar 

  • van de Locht, A., Stubbs, M.T., Bode, W., Friedrich, T., Bollschweiler, C., Hoffken, W. and Huber, R. 1996. The ornithodorin-thrombin crystal structure, a key to the TAP enigma? EMBO J. 15: 6011-6017.

    PubMed  CAS  Google Scholar 

  • Wang, X., Coons, L.B., Taylor, D.B., Stevens, S.E. and 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.

    Article  PubMed  CAS  Google Scholar 

  • Waxman, L. and Connolly, T.M. 1993. Isolation of an inhibitor selective for collagenstimulated platelet aggregation from the soft tick Ornithodoros moubata. J. Biol. Chem. 268: 5445-5449.

    PubMed  CAS  Google Scholar 

  • Zucker, M.B. 1989. Platelet aggregation measured by the photometric method. Method. Enzymol. 169: 117-133.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Albert W.H. Neitz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mans, B.J., Louw, A.I. & Neitz, A.W. Disaggregation of Aggregated Platelets by Savignygrin, a αIIbβ3 Antagonist from Ornithodoros Savignyi . Exp Appl Acarol 27, 231–239 (2002). https://doi.org/10.1023/A:1021613001297

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1021613001297

Navigation