Skip to main content
Log in

Structural characterization of platelets and platelet microvesicles

  • Published:
Cell and Tissue Biology Aims and scope Submit manuscript

Abstract

Platelets are blood cells without nuclei, which, in conjunction with fibrin, cause bleeding to stop (hemostasis). Cellular microvesicles are microscopic particles released into extracellular space under activation and/or apoptosis of cells of different types. Platelet microvesicles form the main population of blood circulating through microvesicles and play an important role in the reactions of hemostasis, thrombosis, and many other (patho)physiological processes. Despite the large number of studies that have been devoted to the function of platelet microvesicles, the mechanisms of their formation and structural details remain poorly understood. The ultrastructure of the initial platelets and microvesicles formed in vitro from resting cells and platelets activated by arachidonic acid, ADP, thrombin, and calcium ionophore A23187 is investigated in this study. The intracellular origin, stages of formation, structural diversity, and size of microvesicles were analyzed according to the results of transmission electron microscopy of human platelets and isolated microvesicles. It was shown that thrombin, unlike other activators, not only stimulates microvesiculation of the plasma membrane, but also causes decomposition of cells with the formation of subcellular particles that have sizes comparable with the size of the microvesicles from the outer membrane of the cells. Some of these microparticles are cellular organelles surrounded by a thin membrane. The size of isolated microvesicles ranges from 30 to 500 nm, but their size distribution depends on the nature of the activating stimulus. The obtained results contain new data on the formation of platelet microvesicles and their structural diversity, which are important for understanding of their multiple functions in health and disease.

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.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

MVs:

microvesicles

OCS:

open canalicular system

PCD:

programmed cell death

References

  • Aatonen, M., Grönholm, M., and Siljander, P.R.-M., Platelet-derived microvesicles: multitalented participants in intercellular communication, Semin. Thromb. Hemos., 2012, vol. 38, pp. 102–113.

    Article  CAS  Google Scholar 

  • Akers, J.C., Gonda, D., Kim, R., Carter, B.S., and Chen, C.C., Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies, J. Neurooncol., 2013, vol. 113, pp. 1–11.

    Article  PubMed  Google Scholar 

  • Arraud, N., Linares, R., Tan, S., Gounou, C., Pasquet, J.-M., Mornet, S., and Brisson, A.R., Extracellular vesicles from blood plasma: determination of their morphology, size, phenotype and concentration, J. Thromb. Haemos., 2014, vol. 12, pp. 614–627.

    Article  CAS  Google Scholar 

  • Ayers, L., Harrison, P., Kohler, M., and Ferry, B., Procoagulant and platelet-derived microvesicle absolute counts determined by flow cytometry correlates with a measurement of their functional capacity, J. Extracell. Vesicles, 2014, vol. 3, p. 25348.

    Article  Google Scholar 

  • Boudreau, L.H., Duchez, A.-C., Cloutier, N., Soulet, D., Martin, N., Bollinger, J., Paré, A., Rousseau, M., Naika, G.S., Lévesque, T., Laflamme, C., Marcoux, G., Lambeau, G., Farndale, R.W., Pouliot, M., HamzehCognasse, H., Cognasse, F., Garraud, O., Nigrovic, P.A., Guderley, H., Lacroix, S., Thibault, L., Semple, J.W., Gelb, M.H., and Boilard, E., Platelets release mitochondria serving as substrate for bactericidal group IIA-secreted phospholipase A2 to promote inflammation, Blood, 2014, vol. 124, pp. 2173–2183.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burnouf, T., Goubran, H.A., Chou, M.L., Devos, D., and Radosevic, M., Platelet microparticles: detection and assessment of their paradoxical functional roles in disease and regenerative medicine, Blood Rev., 2014, vol. 28, pp. 155–166.

    Article  CAS  PubMed  Google Scholar 

  • George, J.N., Thoi, L.L., McManus, L.M., and Reimann, T.A., Isolation of human platelet membrane microparticles from plasma and serum, Blood, 1982, vol. 60, pp. 834–840.

    CAS  PubMed  Google Scholar 

  • Gyulkhandanyan, A.V., Mutlu, A., Freedman, J., and Leytinet, V., Markers of platelet apoptosis: methodology and applications, J. Thromb. Thrombolysis, 2012, vol. 33, pp. 397–411.

    Article  CAS  PubMed  Google Scholar 

  • Heijnen, H.F.G., Schiel, A.E., Fijnheer, R., Geuze, H.J., and Sixma, J.J., Exocytosis of multivesicular bodies and Αgranules microvesicles by surface shedding and exosomes derived from activated platelets release two types of membrane vesicles, Blood, 1999, vol. 94, pp. 3791–3799.

    CAS  PubMed  Google Scholar 

  • James, G. and White, M.D., Exocytosis of secretory organelles from blood platelets incubated with cationic polypeptides, Am J. Pathol., 1972, vol. 69, pp. 41–54.

    Google Scholar 

  • Johnstone, R.M., Adam, M, Hammond, J.R., Orr, L, and Turbide, C., Vesicle formation during reticulocyte maturation, association of plasma membrane activities with released vesicles (exosomes), J. Biol. Chem., 1987, vol. 262, pp. 9412–9420.

    CAS  PubMed  Google Scholar 

  • Kelton, J.G., The pathophysiology of Hepa-induced thrombocytopenia. Biological basis for treatment, Chest, 2005, vol. 127, pp. 9–20.

    Article  Google Scholar 

  • Lacroix, R., Robert, S., Poncelet, P., Kasthuri, R.S., Key, N.S., and Dignat-George, F., Standardization of platelet-derived microparticle enumeration by flow cytometry with calibrated beads: results of the International Society on Thrombosis and Haemostasis SSC Collaborative Workshop, J. Thromb. Haemos., 2010, vol. 8, pp. 2571–2574.

    Article  CAS  Google Scholar 

  • Leytin, V., Allen, D.J., Mykhaylov, S., Lyubimov, E., and Freedman, J., Thrombin-triggered platelet apoptosis, J. Thromb. Haemos., 2006, vol. 4, pp. 2656–2663.

    Article  CAS  Google Scholar 

  • Neumüller, J., Meisslitzer-Ruppitscha, C., Ellinger, A., Pavelkaa, M., Jungbauer, C., Renzb, R., Leitner, G., and Wagner, T., Monitoring of platelet activation in platelet concentrates using transmission electron microscopy, Transfus. Med. Hemother., 2013, vol. 40, pp. 101–107.

    Article  PubMed  PubMed Central  Google Scholar 

  • Nieuwland, R., van, der, Pol, E., Gardiner, C., and Sturk, A., Platelet-derived microparticles, in Platelets, 3rd ed., Amsterdam: Academic Press Elsevier, 2013, vol. 453–467.

    Google Scholar 

  • Nomura, S., Ozaki, Y., and Ikeda, Y., Function and role of microparticles in various clinical settings, Thromb. Res., 2008, vol. 123, pp. 8–23.

    Article  CAS  PubMed  Google Scholar 

  • Nomura, S. and Shimizu, M., Clinical significance of procoagulant microparticles, J. Intens. Care, 2015, vol. 3, pp. 1–11.

    Article  Google Scholar 

  • Owens, A.P. and Mackman, N., Microparticles in hemostasis and thrombosis, Circ. Res., 2011, vol. 108, pp. 1284–1297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Polasek, J., The appearance of multivesicular structures during platelet activation as observed by scanning electron microscopy, Thromb. Res., 1982, vol. 28, pp. 433–437.

    Article  CAS  PubMed  Google Scholar 

  • Stein, J.M. and Luzio, J.P., Ectocytosis caused by sublytic autologous complement attack on human neutrophils. The sorting of endogenous plasma-membrane proteins and lipids into shed vesicles, Biochem. J., 1991, vol. 274, pp. 381–386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thushara, R.M., Hemshekhar, M., Kemparaju, K., Rangappa, K.S., Devaraja, S., and Girish, K.S., Therapeutic drug-induced platelet apoptosis: an overlooked issue in pharmacotoxicology, Arch. Toxicol., 2014, vol. 88, pp. 185–198.

    Article  CAS  PubMed  Google Scholar 

  • Thushara, R.M., Hemshekhar, M., Basappa Kemparaju, K., Rangappa, K.S., and Girish, K.S., Biologicals, platelet apoptosis and human diseases: an outlook, Crit Rev. Oncol. Hematol., 2015, vol. 93, pp. 149–158.

    Article  CAS  PubMed  Google Scholar 

  • Van der Pol, E., Hoekstra, A.G., Sturk, A., Otto, C., Van Leeuwen, T.G., and Nleuwland, R., Optical and nonoptical methods for detection and characterization of microparticles and exosomes, J. Thrombos. Haemos., 2012, vol. 8, pp. 2596–2607.

    Google Scholar 

  • Varon, D. and Shai, E., Platelets and their microparticles as key players in pathophysiological responses, J. Thromb. Haemos., 2015, vol. 13, pp. 40–46.

    Article  Google Scholar 

  • Zucker, W.H., Shermer, R.W., and Mason, R.G., Ultrastructural comparison of human platelets separated from blood by various means, Am. J. Pathol., 1974, vol. 77, pp. 255–268.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zubairov, D.M. and Zubairova, L.D., Mikrovezikuly v krovi. Funktsii i ikh rol' v tromboobrazovanii (Microvesicles in the Blood. The Functions and Their Role in Thrombus Formation), Moscow: GEOTAR-Media, 2009.

    Google Scholar 

  • Zwicker, J.I., Tissue factor-bearing microparticles and cancer, Semin. Thromb. Hemos., 2008, vol. 34, pp. 195–8.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. A. Ponomareva.

Additional information

Original Russian Text © A.A. Ponomareva, T.A. Nevzorova, E.R. Mordakhanova, I.A. Andrianova, R.I. Litvinov, 2016, published in Tsitologiya, 2016, Vol. 58, No. 2, pp. 105–114.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ponomareva, A.A., Nevzorova, T.A., Mordakhanova, E.R. et al. Structural characterization of platelets and platelet microvesicles. Cell Tiss. Biol. 10, 217–226 (2016). https://doi.org/10.1134/S1990519X1603010X

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1990519X1603010X

Keywords

Navigation