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Hematophagy and Inhibition of Platelet Aggregation

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Toxins and Hemostasis

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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.

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Notes

  1. 1.

    Reproduced from Toxicon.

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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.

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  1. Section of Vector Biology, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20852-8132, USA

    Ivo M.B. Francischetti

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  1. , Department of Biological Sciences, National University of Singapore, Science Drive 4 14, Singapore, 117543, Singapore

    R. Manjunatha Kini

  2. , Department of Haematology, University of Berne, Inselspital, Bern, CH-3010, Switzerland

    Kenneth J Clemetson

  3. , Biochemistry and Molecular Biology, University of Southern California, Health Sciences Campus/9270, Los Angeles, 90089, USA

    Francis S. Markland

  4. , Medical Technology, University of Delaware, 305G Willard Hall Educ Bld, Newark, 19716, Delaware, USA

    Mary Ann McLane

  5. , Biochemistry, Meiji Pharmaceutical University, Nishio Kiyose 2-522-1, Tokyo, 204-8588, Japan

    Takashi Morita

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Francischetti, I.M. (2010). Hematophagy and Inhibition of Platelet Aggregation. 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_20

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