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Thromb Haemost 2007; 97(01): 67-80
DOI: 10.1160/TH06-02-0066
Platelets and Blood Cells
Schattauer GmbH

Proteomic discovery of 21 proteins expressed in human plasma-derived but not platelet-derived microparticles

David M. Smalley
1   Mellon Medical Biomarker Discovery Laboratory
2   Robert M. Berne Cardiovascular Research Center
3   Departments of Urology
,
Karen E. Root
1   Mellon Medical Biomarker Discovery Laboratory
3   Departments of Urology
,
HyungJun Cho
5   Public Health Sciences, and
7   Department of Statistics, Korea University, Seoul, Korea
,
Mark M. Ross
1   Mellon Medical Biomarker Discovery Laboratory
3   Departments of Urology
,
Klaus Ley
2   Robert M. Berne Cardiovascular Research Center
4   Biomedical Engineering
6   Molecular Physiology and Biological Physics; University of Virginia, Charlottesville, Virginia, USA
› Author AffiliationsFinancial support: This research was supported by The Mellon Prostate Cancer Center, The Robert M. Berne Cardiovascular Research Center, and the Dean of the School of Medicine at the University of Virginia, USA.
Further Information

Publication History

Received 01 February 2006

Accepted after resubmission 05 November 2006

Publication Date:
28 November 2017 (online)

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Summary

Microparticles (MPs) are small membrane vesicles generated by essentially all cell types. In the plasma, most MPs are derived from platelets, but those from other sources, particularly leukocytes (macrophages, lymphocytes, and neutrophils), endothelial cells, and even smooth muscle cells can be detected and appear to play an important role in normal physiology and various diseases. In previous work we analyzed the proteome of MPs generated from isolated platelets (platelet MPs). Here, we report on a comparative analysis of microparticles isolated from plasma (plasma MPs) versus platelet MP using two complementary methods of comparative analysis. The first method, spectral count analysis, yielded 21 proteins detected in plasma MPs (with a total spectral count of 10 or greater) that were essentially absent in platelet MPs (with a total spectral count of 1 or 0). An additional two proteins (von Willebrand Factor, albumin) were present in both types of MPs but enriched in the plasma MPs. The second method, isotope-coded affinity tag (ICAT) labeling of proteins, supported the spectral count results for the more abundant proteins and provided better relative quantitation of differentially expressed proteins. Proteins present only in the plasma MPs include several associated with apoptosis (CD5-like antigen, galectin 3 binding protein, several complement components), iron transport (transferrin, transferrin receptor, haptoglobin), immune response (complement components, immunoglobulin J and kappa chains), and the coagulation process (protein S, coagulation factor VIII).

Keywords

Secretion / exocytosis - platelet activation markers - vascular cell markers
 

  • References

  • 1 Hugel B, Martinez MC, Kunzelmann C. et al Membrane microparticles: two sides of the coin. Physiology 2005; 20: 22-7.
    CrossrefPubMedSearch in Google Scholar
  • 2 Pilzer D, Gasser O, Moskovich O. et al Emission of membrane vesicles: roles in complement resistance, immunity and cancer. Semin Immunopathol 2005; 1-13.
    PubMedSearch in Google Scholar
  • 3 Wolf P. The nature and significance of platelet products in human plasma. Br J Haematol 1967; 13: 269-88.
    CrossrefPubMedSearch in Google Scholar
  • 4 Horstman LL, Ahn YS. Platelet microparticles: a wide-angle perspective. Crit Rev Oncol Hematol 1999; 30: 111-42.
    CrossrefPubMedSearch in Google Scholar
  • 5 VanWijk MJ, VanBavel E, Sturk A. et al Microparticles in cardiovascular diseases. Cardiovasc Res 2003; 59: 277-87.
    CrossrefPubMedSearch in Google Scholar
  • 6 Mallat Z, Hugel B, Ohan J. et al Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity. Circulation 1999; 99: 348-53.
    CrossrefPubMedSearch in Google Scholar
  • 7 Gasser O, Hess C, Miot S. et al Characterisation and properties of ectosomes released by human polymorphonuclear neutrophils. Exp Cell Res 2003; 285: 243-57.
    CrossrefPubMedSearch in Google Scholar
  • 8 Jimenez JJ, Jy W, Mauro L.. et al Endothelial cells release phenotypically and quantitatively distinct microparticles in activation and apoptosis. Thromb Res 2003; 109: 175-80.
    CrossrefPubMedSearch in Google Scholar
  • 9 Watanabe J, Marathe GK, Neilsen PO. et al Endotoxins stimulate neutrophil adhesion followed by synthesis and release of platelet-activating factor in microparticles. J Biol Chem 2003; 278: 33161-8.
    CrossrefPubMedSearch in Google Scholar
  • 10 MacKenzie A, Wilson HL, Kiss-Toth E. et al Rapid secretion of interleukin-1beta by microvesicle shedding. Immunity 2001; 15: 825-35.
    CrossrefPubMedSearch in Google Scholar
  • 11 Morel O, Toti F, Hugel B. et al Cellular microparticles: a disseminated storage pool of bioactive vascular effectors. Curr Opin Hematol 2004; 11: 156-64.
    CrossrefPubMedSearch in Google Scholar
  • 12 Barry OP, Pratico D, Savani RC. et al Modulation of monocyte-endothelial cell interactions by platelet microparticles. J Clin Invest 1998; 102: 136-44.
    CrossrefPubMedSearch in Google Scholar
  • 13 Mesri M, Altieri DC. Leukocyte microparticles stimulate endothelial cell cytokine release and tissue factor induction in a JNK1 signaling pathway. J Biol Chem 1999; 274: 23111-8.
    CrossrefPubMedSearch in Google Scholar
  • 14 Distler JH, Jungel A, Huber LC. et al The induction of matrix metalloproteinase and cytokine expression in synovial fibroblasts stimulated with immune cell microparticles. Proc Natl Acad Sci USA 2005; 102: 2892-7.
    CrossrefPubMedSearch in Google Scholar
  • 15 Pfister SL. Role of platelet microparticles in the production of thromboxane by rabbit pulmonary artery. Hypertension 2004; 43: 428-33.
    CrossrefPubMedSearch in Google Scholar
  • 16 Brill A, Dashevsky O, Rivo J. et al Platelet-derived microparticles induce angiogenesis and stimulate postischemic revascularization. Cardiovasc Res 2005; 67: 30-8.
    CrossrefPubMedSearch in Google Scholar
  • 17 Gasser O, Schifferli JA. Activated polymorphonuclear neutrophils disseminate anti-inflammatory microparticles by ectocytosis. Blood 2004; 104: 2543-8.
    CrossrefPubMedSearch in Google Scholar
  • 18 Falati S, Liu Q, Gross P. et al Accumulation of tissue factor into developing thrombi in vivo is dependent upon microparticle P-selectin glycoprotein ligand 1 and platelet P-selectin. J Exp Med 2003; 197: 1585-98.
    CrossrefPubMedSearch in Google Scholar
  • 19 Hrachovinova I, Cambien B, Hafezi-Moghadam A. et al Interaction of P-selectin and PSGL-1 generates microparticles that correct hemostasis in a mouse model of hemophilia A. Nat Med 2003; 9: 1020-5.
    CrossrefPubMedSearch in Google Scholar
  • 20 Garcia BA, Smalley DM, Cho H. et al The Platelet Microparticle Proteome. J Proteome Res 2005; 4: 1516-21.
    CrossrefPubMedSearch in Google Scholar
  • 21 Shevchenko A, Wilm M, Vorm O. et al Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Anal Chem 1996; 68: 850-8.
    CrossrefPubMedSearch in Google Scholar
  • 22 Washburn MP, Wolters D, Yates 3rd JR. Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat Biotechnol 2001; 19: 242-7.
    CrossrefPubMedSearch in Google Scholar
  • 23 Palagi PM, Walther D, Quadroni M. et al MSight: an image analysis software for liquid chromatographymass spectrometry. Proteomics 2005; 5: 2381-4.
    CrossrefPubMedSearch in Google Scholar
  • 24 Martinez MC, Tesse A, Zobairi F. et al Shed membrane microparticles from circulating and vascular cells in regulating vascular function. Am J Physiol Heart Circ Physiol 2005; 288: H1004-1009.
    CrossrefPubMedSearch in Google Scholar
  • 25 Forlow SB, McEver RP, Nollert MU. Leukocyteleukocyte interactions mediated by platelet microparticles under flow. Blood 2000; 95: 1317-23.
    CrossrefPubMedSearch in Google Scholar
  • 26 Thery C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol 2002; 2: 569-79.
    CrossrefPubMedSearch in Google Scholar
  • 27 Shet AS, Aras O, Gupta K. et al Sickle blood contains tissue factor-positive microparticles derived from endothelial cells and monocytes. Blood 2003; 102: 2678-83.
    CrossrefPubMedSearch in Google Scholar
  • 28 Jin M, Drwal G, Bourgeois T. et al Distinct proteome features of plasma microparticles. Proteomics 2005; 5: 1940-52.
    CrossrefPubMedSearch in Google Scholar
  • 29 Zellner M, Winkler W, Hayden H. et al Quantitative validation of different protein precipitation methods in proteome analysis of blood platelets. Electrophoresis 2005; 26: 2481-9.
    CrossrefPubMedSearch in Google Scholar
  • 30 Johnstone RM. Revisiting the road to the discovery of exosomes. Blood Cells Mol Dis 2005; 34: 214-9.
    CrossrefPubMedSearch in Google Scholar
  • 31 Fishelson Z, Attali G, Mevorach D. Complement and apoptosis. Mol Immunol 2001; 38: 207-19.
    CrossrefPubMedSearch in Google Scholar
  • 32 Morgan BP. Regulation of the complement membrane attack pathway. Crit Rev Immunol 1999; 19: 173-98.
    CrossrefPubMedSearch in Google Scholar
  • 33 Dighiero G, Rose NR. Critical self-epitopes are key to the understanding of self-tolerance and autoimmunity. Immunol Today 1999; 20: 423-8.
    CrossrefPubMedSearch in Google Scholar
  • 34 Binder CJ, Horkko S, Dewan A. et al Pneumococcal vaccination decreases atherosclerotic lesion formation: molecular mimicry between Streptococcus pneumoniae and oxidized LDL. Nat Med 2003; 9: 736-43.
    CrossrefPubMedSearch in Google Scholar
  • 35 Blom AM, Villoutreix BO, Dahlback B. Complement inhibitor C4b-binding protein-friend or foe in the innate immune system?. Mol Immunol 2004; 40: 1333-46.
    CrossrefPubMedSearch in Google Scholar
  • 36 Anderson HA, Maylock CA, Williams JA. et al Serum-derived protein S binds to phosphatidylserine and stimulates the phagocytosis of apoptotic cells. Nat Immunol 2003; 4: 87-91.
    CrossrefPubMedSearch in Google Scholar
  • 37 Joseph SB, Bradley MN, Castrillo A. et al LXR-dependent gene expression is important for macrophage survival and the innate immune response. Cell 2004; 119: 299-309.
    CrossrefPubMedSearch in Google Scholar
  • 38 Miyazaki T, Hirokami Y, Matsuhashi N. et al Increased susceptibility of thymocytes to apoptosis in mice lacking AIM, a novel murine macrophage-derived soluble factor belonging to the scavenger receptor cysteine-rich domain superfamily. J Exp Med 1999; 189: 413-22.
    CrossrefPubMedSearch in Google Scholar
  • 39 Krzeslak A, Lipinska A. Galectin-3 as a multifunctional protein. Cell Mol Biol Lett 2004; 9: 305-28.
    PubMedSearch in Google Scholar
  • 40 Akahani S, Nangia-Makker P, Inohara H. et al Galectin-3: a novel antiapoptotic molecule with a functional BH1 (NWGR) domain of Bcl-2 family. Cancer Res 1997; 57: 5272-6.
    PubMedSearch in Google Scholar
  • 41 Aisen P. Transferrin receptor 1. Int J Biochem Cell Biol 2004; 36: 2137-43.
    CrossrefPubMedSearch in Google Scholar
  • 42 Pan BT, Teng K, Wu C. et al Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. J Cell Biol 1985; 101: 942-8.
    CrossrefPubMedSearch in Google Scholar
  • 43 Harding C, Heuser J, Stahl P. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J Cell Biol 1983; 97: 329-39.
    CrossrefPubMedSearch in Google Scholar
  • 44 Madsen M, Graversen JH, Moestrup SK. Haptoglobin and CD163: captor and receptor gating hemoglobin to macrophage lysosomes. Redox Rep 2001; 6: 386-8.
    CrossrefPubMedSearch in Google Scholar
  • 45 Lim SK, Kim H, Lim SK. et al Increased susceptibility in Hp knockout mice during acute hemolysis. Blood 1998; 92: 1870-7.
    CrossrefPubMedSearch in Google Scholar
  • 46 Koppelman SJ, Hackeng TM, Sixma JJ. et al Inhibition of the intrinsic factor X activating complex by protein S: evidence for a specific binding of protein S to factor VIII. Blood 1995; 86: 1062-71.
    CrossrefPubMedSearch in Google Scholar
  • 47 Padilla A, Moake JL, Bernardo A. et al P-selectin anchors newly released ultralarge von Willebrand factor multimers to the endothelial cell surface. Blood 2004; 103: 2150-6.
    CrossrefPubMedSearch in Google Scholar
  • 48 Kroll MH, Harris TS, Moake JL. et al von Willebrand factor binding to platelet GpIb initiates signals for platelet activation. J Clin Invest 1991; 88: 1568-73.
    CrossrefPubMedSearch in Google Scholar
  • 49 Goto S, Ikeda Y, Saldivar E. et al Distinct mechanisms of platelet aggregation as a consequence of different shearing flow conditions. J Clin Invest 1998; 101: 479-86.
    CrossrefPubMedSearch in Google Scholar
  • 50 Reininger AJ, Heijnen HF, Schumann H. et al Mechanism of platelet adhesion to von Willebrand factor and microparticle formation under high shear stress. Blood. 2006
    CrossrefSearch in Google Scholar
  • 51 Jimenez JJ, Jy W, Mauro LM, Horstman LL. et al Endothelial microparticles released in thrombotic thrombocytopenic purpura express von Willebrand factor and markers of endothelial activation. Br J Haematol 2003; 123: 896-902.
    CrossrefPubMedSearch in Google Scholar
  • 52 Lopez JA, Dong JF. Cleavage of von Willebrand factor by ADAMTS-13 on endothelial cells. Semin Hematol 2004; 41: 15-23.
    CrossrefPubMedSearch in Google Scholar
  • 53 Rubin DC, Swietlicki EA, Iordanov H. et al Novel goblet cell gene related to IgGFc? BP is regulated in adapting gut after small bowel resection. Am J Physiol Gastrointest Liver Physiol 2000; 279: G1003-1010.
    CrossrefPubMedSearch in Google Scholar
  • 54 Harada N, Iijima S, Kobayashi K. et al Human IgGFc binding protein (Fc? BP) in colonic epithelial cells exhibits mucin-like structure. J Biol Chem 1997; 272: 15232-41.
    CrossrefPubMedSearch in Google Scholar
  • 55 Kobayashi K, Ogata H, Morikawa M. et al Distribution and partial characterisation of IgG Fc binding protein in various mucin producing cells and body fluids. Gut 2002; 51: 169-76.
    CrossrefPubMedSearch in Google Scholar
  • 56 Hsia HC, Schwarzbauer JE. Meet the tenascins: multifunctional and mysterious. J Biol Chem 2005; 280: 26641-4.
    CrossrefPubMedSearch in Google Scholar
  • 57 Schecter AD, Spirn B, Rossikhina M. et al Release of active tissue factor by human arterial smooth muscle cells. Circ Res 2000; 87: 126-32.
    CrossrefPubMedSearch in Google Scholar
  • 58 Martin DM, Boys CW, Ruf W. Tissue factor: molecular recognition and cofactor function. Faseb J 1995; 9: 852-9.
    CrossrefPubMedSearch in Google Scholar