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Proteomics of Blood-Based Therapeutics

A Promising Tool for Quality Assurance in Transfusion Medicine

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Abstract

Blood-based therapeutics are cellular or plasma components derived from human blood. Their production requires appropriate selection and treatment of the donor and processing of cells or plasma proteins. In contrast to clearly defined, chemically synthesized drugs, blood-derived therapeutics are highly complex mixtures of plasma proteins or even more complex cells. Pathogen transmission by the product as well as changes in the integrity of blood constituents resulting in loss of function or immune modulation are currently important issues in transfusion medicine. Protein modifications can occur during various steps of the production process, such as acquisition, enrichment of separate components (e.g. coagulation factors, cell populations), virus inactivation, conservation, and storage.

Contemporary proteomic strategies allow a comprehensive assessment of protein modifications with high coverage, offer capabilities for qualitative and even quantitative analysis, and for high-throughput protein identification. Traditionally, proteomics approaches predominantly relied on two-dimensional gel electrophoresis (2-DE). Even if 2-DE is still state of the art, it has inherent limitations that are mainly based on the physicochemical properties of the proteins analyzed; for example, proteins with extremes in molecular mass and hydrophobicity (most membrane proteins) are difficult to assess by 2-DE. These limitations have fostered the development of mass spectrometry centered on non-gel-based separation approaches, which have proven to be highly successful and are thus complementing and even partially replacing 2-DE-based approaches.

Although blood constituents have been extensively analyzed by proteomics, this technology has not been widely applied to assess or even improve blood-derived therapeutics, or to monitor the production processes. As proteomic technologies have the capacity to provide comprehensive information about changes occurring during processing and storage of blood products, proteomics can potentially guide improvement of pathogen inactivation procedures and engineering of stem cells, and may also allow a better understanding of factors influencing the immunogenicity of blood-derived therapeutics. An important development in proteomics is the reduction of inter-assay variability. This now allows the screening of samples taken from the same product over time or before and after processing. Optimized preparation procedures and storage conditions will reduce the risk of protein alterations, which in turn may contribute to better recovery, reduced exposure to allogeneic proteins, and increased transfusion safety.

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References

  1. Greinacher A, Warkentin TE. Transfusion medicine in the era of genomics and proteomics. Transfus Med Rev 2005; 19(4): 288–94

    Article  PubMed  Google Scholar 

  2. Klose J. Protein mapping by combined isoelectric focusing and electrophoresis of mouse tissues: a novel approach to testing for induced point mutations in mammals. Humangenetik 1975; 26(3): 231–43

    PubMed  CAS  Google Scholar 

  3. O’Farrell PH. High resolution two-dimensional electrophoresis of proteins. J Biol Chem1975; 250(10): 4007–21

    PubMed  Google Scholar 

  4. Cristea IM, Gaskell SJ, Whetton AD. Proteomics techniques and their application to hematology. Blood 2004; 103(10): 3624–34

    Article  PubMed  CAS  Google Scholar 

  5. Thadikkaran L, Siegenthaler MA, Crettaz D, et al. Recent advances in blood-related proteomics. Proteomics 2005; 5(12): 3019–34

    Article  PubMed  CAS  Google Scholar 

  6. Reddy KS, Perrotta PL. Proteomics in transfusion medicine. Transfusion 2004; 44(4): 601–4

    Article  PubMed  Google Scholar 

  7. Queloz PA, Thadikkaran L, Crettaz D, et al. Proteomics and transfusion medicine: future perspectives. Proteomics 2006; 6(20): 5605–14

    Article  PubMed  CAS  Google Scholar 

  8. Page MJ, Griffiths TA, Bleackley MR, et al. Proteomics: applications relevant to transfusion medicine. Transfus Med Rev 2006; 20(1): 63–74

    Article  PubMed  Google Scholar 

  9. Bjellqvist B, Ek K, Righetti PG, et al. Isoelectric focusing in immobilized pH gradients: principle, methodology and some applications. J Biochem Biophys Methods 1982; 6(4): 317–39

    Article  PubMed  CAS  Google Scholar 

  10. Gorg A, Weser J, Westermeier R, et al. Isoelectric focusing with immobilized pH gradients for the analysis of transferrin (Tf) subtypes and variants. Hum Genet 1983; 64(3): 222–6

    Article  PubMed  CAS  Google Scholar 

  11. Diezel W, Kopperschlager G, Hofmann E. An improved procedure for protein staining in polyacrylamide gels with a new type of Coomassie Brilliant Blue. Anal Biochem 1972; 48(2): 617–20

    Article  PubMed  CAS  Google Scholar 

  12. Berggren KN, Schulenberg B, Lopez MF, et al. An improved formulation of SYPRO Ruby protein gel stain: comparison with the original formulation and with a ruthenium II tris (bathophenanthroline disulfonate) formulation. Proteomics 2002; 2(5): 486–98

    Article  PubMed  CAS  Google Scholar 

  13. Lopez MF, Berggren K, Chernokalskaya E, et al. A comparison of silver stain and SYPRO ruby protein gel stain with respect to protein detection in two-dimensional gels and identification by peptide mass profiling. Electrophoresis 2000; 21(17): 3673–83

    Article  PubMed  CAS  Google Scholar 

  14. Lanne B, Panfilov O. Protein staining influences the quality of mass spectra obtained by peptide mass fingerprinting after separation on 2-d gels: a comparison of staining with coomassie brilliant blue and sypro ruby. J Proteome Res 2005; 4(1): 175–9

    Article  PubMed  CAS  Google Scholar 

  15. Benga G, Banner M, Wrigglesworth JM. Quantitation of the water channel protein aquaporin (CHIP28) from red blood cell membranes by densitometry of silver stained polyacrylamide gels. Electrophoresis 1996; 17(4): 715–9

    Article  PubMed  CAS  Google Scholar 

  16. Dutt MJ, Lee KH. The scaled volume as an image analysis variable for detecting changes in protein expression levels by silver stain. Electrophoresis 2001; 22(9): 1627–32

    Article  PubMed  CAS  Google Scholar 

  17. Rabilloud T. Mechanisms of protein silver staining in polyacrylamide gels: a 10-year synthesis. Electrophoresis 1990; 11(10): 785–94

    Article  PubMed  CAS  Google Scholar 

  18. Yan JX, Wait R, Berkelman T, et al. A modified silver staining protocol for visualization of proteins compatible with matrix-assisted laser desorption/ ionization and electrospray ionization-mass spectrometry. Electrophoresis 2000; 21(17): 3666–72

    Article  PubMed  CAS  Google Scholar 

  19. Nishihara JC, Champion KM. Quantitative evaluation of proteins in one- and two-dimensional polyacrylamide gels using a fluorescent stain. Electrophoresis 2002; 23(14): 2203–15

    Article  PubMed  CAS  Google Scholar 

  20. Yan JX, Harry RA, Spibey C, et al. Postelectrophoretic staining of proteins separated by two-dimensional gel electrophoresis using SYPRO dyes. Electrophoresis 2000; 21(17): 3657–65

    Article  PubMed  CAS  Google Scholar 

  21. Unlu M, Morgan ME, Minden JS. Difference gel electrophoresis: a single gel method for detecting changes in protein extracts. Electrophoresis 1997; 18(11): 2071–7

    Article  PubMed  CAS  Google Scholar 

  22. Alban A, David SO, Bjorkesten L, et al. A novel experimental design for comparative two-dimensional gel analysis: two-dimensional difference gel electrophoresis incorporating a pooled internal standard. Proteomics 2003; 3(1): 36–44

    Article  PubMed  CAS  Google Scholar 

  23. Shaw J, Rowlinson R, Nickson J, et al. Evaluation of saturation labelling two-dimensional difference gel electrophoresis fluorescent dyes. Proteomics 2003; 3(7): 1181–95

    Article  PubMed  CAS  Google Scholar 

  24. Steinberg TH, Agnew BJ, Gee KR, et al. Global quantitative phosphoprotein analysis using multiplexed proteomics technology. Proteomics 2003; 3(7): 1128–44

    Article  PubMed  CAS  Google Scholar 

  25. Morandell S, Stasyk T, Grosstessner-Hain K, et al. Phosphoproteomics strategies for the functional analysis of signal transduction. Proteomics 2006; 6(14): 4047–56

    Article  PubMed  CAS  Google Scholar 

  26. Agrawal GK, Thelen JJ. Development of a simplified, economical polyacrylamide gel staining protocol for phosphoproteins. Proteomics 2005; 5(18): 4684–8

    Article  PubMed  CAS  Google Scholar 

  27. Coghlan DR, Mackintosh JA, Karuso P. Mechanism of reversible fluorescent staining of protein with epicocconone. Org Lett 2005; 7(12): 2401–4

    Article  PubMed  CAS  Google Scholar 

  28. Mackintosh JA, Choi HY, Bae SH, et al. A fluorescent natural product for ultra sensitive detection of proteins in one-dimensional and two-dimensional gel electrophoresis. Proteomics 2003; 3(12): 2273–88

    Article  PubMed  CAS  Google Scholar 

  29. Bell PJ, Karuso P. Epicocconone, a novel fluorescent compound from the fungus epicoccumnigrum. J Am Chem Soc 2003; 125(31): 9304–5

    Article  PubMed  CAS  Google Scholar 

  30. Tokarski C, Cren-Olive C, Fillet M, et al. High-sensitivity staining of proteins for one- and two-dimensional gel electrophoresis using post migration covalent staining with a ruthenium fluorophore. Electrophoresis 2006; 27(7): 1407–16

    Article  PubMed  CAS  Google Scholar 

  31. Lecocq R, Lamy F, Dumont JE. Use of two-dimensional gel electrophoresis and autoradiography as a tool in cell biology: the example of the thyroid and the liver. Electrophoresis 1990; 11(3): 200–12

    Article  PubMed  CAS  Google Scholar 

  32. Kaufmann H, Bailey JE, Fussenegger M. Use of antibodies for detection of phosphorylated proteins separated by two-dimensional gel electrophoresis. Proteomics 2001; 1(2): 194–9

    Article  PubMed  CAS  Google Scholar 

  33. Sickmann A, Meyer HE. Phosphoamino acid analysis. Proteomics 2001; 1(2): 200–6

    Article  PubMed  CAS  Google Scholar 

  34. Gronborg M, Kristiansen TZ, Stensballe A, et al. A mass spectrometry-based proteomic approach for identification of serine/threonine-phosphorylated proteins by enrichment with phospho-specific antibodies: identification of a novel protein, Frigg, as a protein kinase A substrate. Mol Cell Proteomics 2002; 1(7): 517–27

    Article  PubMed  CAS  Google Scholar 

  35. Raggiaschi R, Gotta S, Terstappen GC. Phosphoproteome analysis. Biosci Rep 2005; 25(1–2): 33–44

    Article  PubMed  CAS  Google Scholar 

  36. Volker U, Hecker M. From genomics via proteomics to cellular physiology of the Gram-positive model organism Bacillus subtilis. Cell Microbiol 2005; 7(8): 1077–85

    Article  PubMed  CAS  Google Scholar 

  37. Anderson NL, Anderson NG. The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics 2002; 1(11): 845–67

    Article  PubMed  CAS  Google Scholar 

  38. Chromy BA, Gonzales AD, Perkins J, et al. Proteomic analysis of human serum by two-dimensional differential gel electrophoresis after depletion of high-abundant proteins. J Proteome Res 2004; 3(6): 1120–7

    Article  PubMed  CAS  Google Scholar 

  39. Ahmed N, Barker G, Oliva K, et al. An approach to remove albumin for the proteomic analysis of low abundance biomarkers in human serum. Proteomics 2003; 3(10): 1980–7

    Article  PubMed  CAS  Google Scholar 

  40. Gorg A, Weiss W, Dunn MJ. Current two-dimensional electrophoresis technology for proteomics. Proteomics 2004; 4(12): 3665–85

    Article  PubMed  CAS  Google Scholar 

  41. Mitchell P. In the pursuit of industrial proteomics. Nat Biotechnol 2003; 21(3): 233–7

    Article  PubMed  CAS  Google Scholar 

  42. Rabilloud T. Two-dimensional gel electrophoresis in proteomics: old, old fashioned, but it still climbs up the mountains. Proteomics 2002; 2(1): 3–10

    Article  PubMed  CAS  Google Scholar 

  43. Aebersold R, Mann M. Mass spectrometry-based proteomics. Nature 2003; 422(6928): 198–207

    Article  PubMed  CAS  Google Scholar 

  44. Stasyk T, Huber LA. Zooming in: fractionation strategies in proteomics. Proteomics 2004; 4(12): 3704–16

    Article  PubMed  CAS  Google Scholar 

  45. Martosella J, Zolotarjova N, Liu H, et al. Reversed-phase high-performance liquid chromatographic prefractionation of immunodepleted human serum proteins to enhance mass spectrometry identification of lower-abundant proteins. J Proteome Res 2005; 4(5): 1522–37

    Article  PubMed  CAS  Google Scholar 

  46. Wu SL, Kim J, Hancock WS, et al. Extended range proteomic analysis (ERPA): a new and sensitive LC-MS platform for high sequence coverage of complex proteins with extensive post-translational modifications-comprehensive analysis of beta-casein and epidermal growth factor receptor (EGFR). J Proteome Res 2005; 4(4): 1155–70

    Article  PubMed  CAS  Google Scholar 

  47. Link AJ, Eng J, Schieltz DM, et al. Direct analysis of protein complexes using mass spectrometry. Nat Biotechnol 1999; 17(7): 676–82

    Article  PubMed  CAS  Google Scholar 

  48. Washburn MP, Wolters D, Yates JR III. Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat Biotechnol 2001; 19(3): 242–7

    Article  PubMed  CAS  Google Scholar 

  49. Kislinger T, Gramolini AO, MacLennan DH, et al. Multidimensional protein identification technology (MudPIT): technical overview of a profiling method optimized for the comprehensive proteomic investigation of normal and diseased heart tissue. J Am Soc Mass Spectrom 2005; 16(8): 1207–20

    Article  PubMed  CAS  Google Scholar 

  50. Peng J, Elias JE, Thoreen CC, et al. Evaluation of multidimensional chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) for large-scale protein analysis: the yeast proteome. J Proteome Res 2003; 2(1): 43–50

    Article  PubMed  CAS  Google Scholar 

  51. Gevaert K, Van Damme J, Goethals M, et al. Chromatographic isolation of methionine-containing peptides for gel-free proteome analysis: identification of more than 800 Escherichia coli proteins. Mol Cell Proteomics 2002; 1(11): 896–903

    Article  PubMed  CAS  Google Scholar 

  52. Gevaert K, Goethals M, Martens L, et al. Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol 2003; 21(5): 566–9

    Article  PubMed  CAS  Google Scholar 

  53. McCormack AL, Schieltz DM, Goode B, et al. Direct analysis and identification of proteins in mixtures by LC/MS/MS and database searching at the low-femtomole level. Anal Chem 1997; 69(4): 767–76

    Article  PubMed  CAS  Google Scholar 

  54. Haas W, Faherty BK, Gerber SA, et al. Optimization and use of peptide mass measurement accuracy in shotgun proteomics. Mol Cell Proteomics 2006; 5(7): 1326–37

    Article  PubMed  CAS  Google Scholar 

  55. Foster LJ, deHoog CL, Zhang Y, et al. A mammalian organelle map by protein correlation profiling. Cell 2006; 125(1): 187–99

    Article  PubMed  CAS  Google Scholar 

  56. Becker D, Selbach M, Rollenhagen C, et al. Robust Salmonella metabolism limits possibilities for new antimicrobials. Nature 2006; 440(7082): 303–7

    Article  PubMed  CAS  Google Scholar 

  57. Pasini EM, Kirkegaard M, Mortensen P, et al. In-depth analysis of the membrane and cytosolic proteome of red blood cells. Blood 2006; 108(3): 791–801

    Article  PubMed  CAS  Google Scholar 

  58. Ong SE, Blagoev B, Kratchmarova I, et al. Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics 2002; 1(5): 376–86

    Article  PubMed  CAS  Google Scholar 

  59. Gygi SP, Rist B, Gerber SA, et al. Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat Biotechnol 1999; 17(10): 994–9

    Article  PubMed  CAS  Google Scholar 

  60. Leitner A, Lindner W. Current chemical tagging strategies for proteome analysis by mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2004; 813(1–2): 1–26

    PubMed  CAS  Google Scholar 

  61. Ross PL, Huang YN, Marchese JN, et al. Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Mol Cell Proteomics 2004; 3(12): 1154–69

    Article  PubMed  CAS  Google Scholar 

  62. Meyerzu Schwabedissen HE, Dreisbach A, Hammer E, et al. Direct mass spectrometric identification of ABCB1 (P-glycoprotein/MDR1) from the apical membrane fraction of human placenta using fourier transform ion cyclotron mass spectrometry. Pharmacogenet Genomics 2006; 16(6): 385–9

    Article  CAS  Google Scholar 

  63. Reinders J, Lewandrowski U, Moebius J, et al. Challenges in mass spectrometry-based proteomics. Proteomics 2004; 4(12): 3686–703

    Article  PubMed  CAS  Google Scholar 

  64. Putz S, Reinders J, Reinders Y, et al. Mass spectrometry-based peptide quantification: applications and limitations. Expert Rev Proteomics 2005; 2(3): 381–92

    Article  PubMed  Google Scholar 

  65. Wolff S, Otto A, Albrecht D, et al. Gel-free and gel-based proteomics in Bacillus subtilis: a comparative study. Mol Cell Proteomics 2006; 5(7): 1183–92

    Article  PubMed  CAS  Google Scholar 

  66. Wu WW, Wang G, Baek SJ, et al. Comparative study of three proteomic quantitative methods, DIGE, cICAT, and iTRAQ, using 2D gel- or LC-MALDI TOF/TOF. J Proteome Res 2006; 5(3): 651–8

    Article  PubMed  CAS  Google Scholar 

  67. Biondi C, Cotorruelo C, Ensinck A, et al. Senescent erythrocytes: factors affecting the aging of red blood cells. Immunol Invest 2002; 31(1): 41–50

    Article  PubMed  CAS  Google Scholar 

  68. Hess JR. An update on solutions for red cell storage. Vox Sang 2006; 91(1): 13–9

    Article  PubMed  CAS  Google Scholar 

  69. Anderson KC, Goodnough LT, Sayers M, et al. Variation in blood component irradiation practice: implications for prevention of transfusion-associated graft-versus-host disease. Blood 1991; 77(10): 2096–102

    PubMed  CAS  Google Scholar 

  70. deKorte D, Verhoeven AJ. Quality determinants of erythrocyte destined for transfusion. Cell Mol Biol (Noisy-le-grand) 2004; 50(2): 187–95

    Google Scholar 

  71. Rosenblum BB. Two-dimensional gel electrophoresis of erythrocyte membrane proteins. Prog Clin Biol Res 1981; 56: 251–68

    PubMed  CAS  Google Scholar 

  72. Aminoff D, Rolfes-curl A, Supina E. Molecular biomarkers of aging: the red cell as a model. Arch Gerontology Geriatrics 1992; 15Suppl. 1: 7–15

    Article  Google Scholar 

  73. Low TY, Seow TK, Chung MC. Separation of human erythrocyte membrane associated proteins with one-dimensional and two-dimensional gel electrophoresis followed by identification with matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Proteomics 2002; 2(9): 1229–39

    Article  PubMed  CAS  Google Scholar 

  74. Kakhniashvili DG, Bulla LA Jr, Goodman SR. The human erythrocyte proteome: analysis by ion trap mass spectrometry. Mol Cell Proteomics 2004; 3(5): 501–9

    Article  PubMed  CAS  Google Scholar 

  75. Kakhniashvili DG, Griko NB, Bulla LA Jr, et al. The proteomics of sickle cell disease: profiling of erythrocyte membrane proteins by 2D-DIGE and tandem mass spectrometry. Exp Biol Med (Maywood) 2005; 230(11): 787–92

    CAS  Google Scholar 

  76. Korbel S, Buchse T, Prietzsch H, et al. Phosphoprotein profiling of erythropoietin receptor-dependent pathways using different proteomic strategies. Proteomics 2005; 5(1): 91–100

    Article  PubMed  CAS  Google Scholar 

  77. Florens L, Liu X, Wang Y, et al. Proteomics approach reveals novel proteins on the surface of malaria-infected erythrocytes. Mol Biochem Parasitol 2004; 135(1): 1–11

    Article  PubMed  CAS  Google Scholar 

  78. Florens L, Washburn MP, Raine JD, et al. A proteomic view of the Plasmodium falciparum life cycle. Nature 2002; 419(6906): 520–6

    Article  PubMed  CAS  Google Scholar 

  79. Jiang M, Jia L, Jiang W, et al. Protein disregulation in red blood cell membranes of type 2 diabetic patients. Biochem Biophys Res Commun 2003; 309(1): 196–200

    Article  PubMed  CAS  Google Scholar 

  80. Brand M, Ranish JA, Kummer NT, et al. Dynamic changes in transcription factor complexes during erythroid differentiation revealed by quantitative proteomics. Nat Struct Mol Biol 2004; 11(1): 73–80

    Article  PubMed  CAS  Google Scholar 

  81. Tyan YC, Liao JD, Jong SB, et al. Proteomic profiling of platelet proteins by trypsin immobilized self-assembled monolayers digestion chip and protein identification using electrospray ionization tandem mass spectrometry. J Biomed Mater Res A2004; 71(1): 90–7

    Article  PubMed  CAS  Google Scholar 

  82. Anniss AM, Glenister KM, Killian JJ, et al. Proteomic analysis of supernatants of stored red blood cell products. Transfusion 2005; 45(9): 1426–33

    Article  PubMed  CAS  Google Scholar 

  83. Bugert P, Dugrillon A, Gunaydin A, et al. Messenger RNA profiling of human platelets by microarray hybridization. Thromb Haemost 2003; 90(4): 738–48

    PubMed  CAS  Google Scholar 

  84. Weyrich AS, Zimmerman GA. Platelets: signaling cells in the immune continuum. Trends Immunol 2004; 25(9): 489–95

    Article  PubMed  CAS  Google Scholar 

  85. Nurden AT, Nurden P. Inherited disorders of platelets: an update. Curr Opin Hematol 2006; 13(3): 157–62

    Article  PubMed  CAS  Google Scholar 

  86. Murphy S. Platelets from pooled buffy coats: an update. Transfusion 2005; 45(4): 634–9

    Article  PubMed  Google Scholar 

  87. Holme S, Vaidja K, Murphy S. Platelet storage at 22 degrees C: effect of type of agitation on morphology, viability, and function in vitro. Blood 1978; 52(2): 425–35

    PubMed  CAS  Google Scholar 

  88. Klinger MH. The storage lesion of platelets: ultrastructural and functional aspects. Ann Hematol 1996; 73(3): 103–12

    Article  PubMed  CAS  Google Scholar 

  89. Seghatchian J, Krailadsiri P. The platelet storage lesion. Transfus Med Rev 1997; 11(2): 130–44

    Article  PubMed  CAS  Google Scholar 

  90. Cardigan R, Turner C, Harrison P. Current methods of assessing platelet function: relevance to transfusion medicine. Vox Sang 2005; 88(3): 153–63

    Article  PubMed  CAS  Google Scholar 

  91. Clemetson KJ, Capitanio A, Luscher EF. High resolution two-dimensional gel electrophoresis of the proteins and glycoproteins of human blood platelets and platelet membranes. Biochim Biophys Acta 1979; 553(1): 11–24

    Article  PubMed  CAS  Google Scholar 

  92. Garcia A, Watson SP, Dwek RA, et al. Applying proteomics technology to platelet research. Mass Spectrom Rev 2005; 24(6): 918–30

    Article  PubMed  CAS  Google Scholar 

  93. Macaulay IC, Carr P, Gusnanto A, et al. Platelet genomics and proteomics in human health and disease. J Clin Invest 2005; 115(12): 3370–7

    Article  PubMed  CAS  Google Scholar 

  94. Maguire PB, Moran N, Cagney G, et al. Application of proteomics to the study of platelet regulatory mechanisms. Trends Cardiovasc Med 2004; 14(6): 207–20

    Article  PubMed  CAS  Google Scholar 

  95. McRedmond JP, Park SD, Reilly DF, et al. Integration of proteomics and genomics in platelets: a profile of platelet proteins and platelet-specific genes. Mol Cell Proteomics 2004; 3(2): 133–44

    PubMed  CAS  Google Scholar 

  96. Gravel P, Sanchez JC, Walzer C, et al. Human blood platelet protein map established by two-dimensional polyacrylamide gel electrophoresis. Electrophoresis 1995; 16(7): 1152–9

    Article  PubMed  CAS  Google Scholar 

  97. Immler D, Gremm D, Kirsch D, et al. Identification of phosphorylated proteins from thrombin-activated human platelets isolated by two-dimensional gel electrophoresis by electrospray ionization-tandem mass spectrometry (ESI-MS/ MS) and liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). Electrophoresis 1998; 19(6): 1015–23

    Article  PubMed  CAS  Google Scholar 

  98. Marcus K, Immler D, Sternberger J, et al. Identification of platelet proteins separated by two-dimensional gel electrophoresis and analyzed by matrix assisted laser desorption/ionization-time of flight-mass spectrometry and detection of tyrosine-phosphorylated proteins. Electrophoresis 2000; 21(13): 2622–36

    Article  PubMed  CAS  Google Scholar 

  99. O’Neill EE, Brock CJ, von Kriegsheim AF, et al. Towards complete analysis of the platelet proteome. Proteomics 2002; 2(3): 288–305

    Article  PubMed  Google Scholar 

  100. Garcia A, Prabhakar S, Brock CJ, et al. Extensive analysis of the human platelet proteome by two-dimensional gel electrophoresis and mass spectrometry. Proteomics 2004; 4(3): 656–68

    Article  PubMed  CAS  Google Scholar 

  101. Maguire PB, Wynne KJ, Harney DF, et al. Identification of the phosphotyrosine proteome from thrombin activated platelets. Proteomics 2002; 2(6): 642–8

    Article  PubMed  CAS  Google Scholar 

  102. Marcus K, Moebius J, Meyer HE. Differential analysis of phosphorylated proteins in resting and thrombin-stimulated human platelets. Anal Bioanal Chem2003; 376(7): 973–93

    Article  PubMed  CAS  Google Scholar 

  103. Garcia A, Prabhakar S, Hughan S, et al. Differential proteome analysis of TRAP-activated platelets: involvement of DOK-2 and phosphorylation of RGS proteins. Blood 2004; 103(6): 2088–95

    Article  PubMed  CAS  Google Scholar 

  104. Garcia A, Senis YA, Antrobus R, et al. A global proteomics approach identifies novel phosphorylated signaling proteins in GPVI-activated platelets: involvement of G6f, a novel platelet Grb2-binding membrane adapter. Proteomics 2006; 6(19): 5332–43

    Article  PubMed  CAS  Google Scholar 

  105. Lewandrowski U, Moebius J, Walter U, et al. Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach. Mol Cell Proteomics 2006; 5(2): 226–33

    PubMed  CAS  Google Scholar 

  106. Moebius J, Zahedi RP, Lewandrowski U, et al. The human platelet membrane proteome reveals several new potential membrane proteins. Mol Cell Proteomics 2005; 4(11): 1754–61

    Article  PubMed  CAS  Google Scholar 

  107. Garcia A, Zitzmann N, Watson SP. Analyzing the platelet proteome. Semin Thromb Hemost 2004; 30(4): 485–9

    Article  PubMed  CAS  Google Scholar 

  108. Coppinger JA, Cagney G, Toomey S, et al. Characterization of the proteins released from activated platelets leads to localization of novel platelet proteins in human atherosclerotic lesions. Blood 2004; 103(6): 2096–104

    Article  PubMed  CAS  Google Scholar 

  109. Garcia BA, Smalley DM, Cho H, et al. The platelet microparticle proteome. J Proteome Res 2005; 4(5): 1516–21

    Article  PubMed  CAS  Google Scholar 

  110. Martens L, Van Damme P, Van Damme J, et al. The human platelet proteome mapped by peptide-centric proteomics: a functional protein profile. Proteomics 2005; 5(12): 3193–204

    Article  PubMed  CAS  Google Scholar 

  111. Staes A, Demol H, Van Damme J, et al. Global differential non-gel proteomics by quantitative and stable labeling of tryptic peptides with oxygen-18. J Proteome Res 2004; 3(4): 786–91

    Article  PubMed  CAS  Google Scholar 

  112. Dittrich M, Birschmann I, Stuhlfelder C, et al. Understanding platelets. Lessons from proteomics, genomics and promises from network analysis. Thromb Haemost 2005; 94(5): 916–25

    PubMed  CAS  Google Scholar 

  113. Snyder EL, Dunn BE, Giometti CS, et al. Protein changes occurring during storage of platelet concentrates: a two-dimensional gel electrophoretic analysis. Transfusion 1987; 27(4): 335–41

    Article  PubMed  CAS  Google Scholar 

  114. Snyder EL, Horne WC, Napychank P, et al. Calcium-dependent proteolysis of actin during storage of platelet concentrates. Blood 1989; 73(5): 1380–5

    PubMed  CAS  Google Scholar 

  115. Estebanell E, Diaz-Ricart M, Lozano M, et al. Cytoskeletal reorganization after preparation of platelet concentrates, using the buffy coat method, and during their storage. Haematologica 1998; 83(2): 112–7

    PubMed  CAS  Google Scholar 

  116. Thiele T, Steil L, Gebhard S, et al. Profiling of alterations in platelet proteins during storage of platelet concentrates. Transfusion. In press

  117. Gulliksson H. Defining the optimal storage conditions for the long-term storage of platelets. Transfus Med Rev 2003; 17(3): 209–15

    Article  PubMed  Google Scholar 

  118. Heuft HG, Goudeva L, Blasczyk R. A comparative study of adverse reactions occurring after administration of glycosylated granulocyte colony stimulating factor and/or dexamethasone for mobilization of neutrophils in healthy donors. Ann Hematol 2004; 83(5): 279–85

    Article  PubMed  CAS  Google Scholar 

  119. Hubel K, Rodger E, Gaviria JM, et al. Effective storage of granulocytes collected by centrifugation leukapheresis from donors stimulated with granulocyte-colony-stimulating factor. Transfusion 2005; 45(12): 1876–89

    Article  PubMed  CAS  Google Scholar 

  120. Lominadze G, Ward RA, Klein JB, et al. Proteomic analysis of human neutrophils. Methods Mol Biol 2006; 332: 343–56

    PubMed  CAS  Google Scholar 

  121. Boussac M, Garin J. Calcium-dependent secretion in human neutrophils: a proteomic approach. Electrophoresis 2000; 21(3): 665–72

    Article  PubMed  CAS  Google Scholar 

  122. Avram D, Romijn EP, Pap EH, et al. Identification of proteins in activated human neutrophils susceptible to tyrosyl radical attack: a proteomic study using a tyrosylating fluorophore. Proteomics 2004; 4(8): 2397–407

    Article  PubMed  CAS  Google Scholar 

  123. Lominadze G, Powell DW, Luerman GC, et al. Proteomic analysis of human neutrophil granules. Mol Cell Proteomics 2005; 4(10): 1503–21

    Article  PubMed  CAS  Google Scholar 

  124. Singh S, Powell DW, Rane MJ, et al. Identification of the p16-Arc subunit of the Arp 2/3 complex as a substrate of MAPK-activated protein kinase 2 by proteomic analysis. J Biol Chem 2003; 278(38): 36410–7

    Article  PubMed  CAS  Google Scholar 

  125. Takahashi S, Iseki T, Ooi J, et al. Single-institute comparative analysis of unrelated bone marrow transplantation and cord blood transplantation for adult patients with hematologic malignancies. Blood 2004; 104(12): 3813–20

    Article  PubMed  CAS  Google Scholar 

  126. Li X, Le Beau MM, Ciccone S, et al. Ex vivo culture of Fancc−/− stem/progenitor cells predisposes cells to undergo apoptosis, and surviving stem/progenitor cells display cytogenetic abnormalities and an increased risk of malignancy. Blood 2005; 105(9): 3465–71

    Article  PubMed  CAS  Google Scholar 

  127. Hubel A, Carlquist D, Clay M, et al. Short-term liquid storage of umbilical cord blood. Transfusion 2003; 43(5): 626–32

    Article  PubMed  Google Scholar 

  128. Bosse R, Kulmburg P, von Kalle C, et al. Production of stem-cell transplants according to good manufacturing practice. Ann Hematol 2000; 79(9): 469–76

    Article  PubMed  CAS  Google Scholar 

  129. Herve P. Donor-derived hematopoietic stem cells in organ transplantation: technical aspects and hurdles yet to be cleared. Transplantation 2003; 75(9 Suppl.): 55S–7S

    Article  PubMed  Google Scholar 

  130. Lian Z, Wang L, Yamaga S, et al. Genomic and proteomic analysis of the myeloid differentiation program. Blood 2001; 98(3): 513–24

    Article  PubMed  CAS  Google Scholar 

  131. Lian Z, Kluger Y, Greenbaum DS, et al. Genomic and proteomic analysis of the myeloid differentiation program: global analysis of gene expression during induced differentiation in the MPRO cell line. Blood 2002; 100(9): 3209–20

    Article  PubMed  CAS  Google Scholar 

  132. Tian Q, Stepaniants SB, Mao M, et al. Integrated genomic and proteomic analyses of gene expression in mammalian cells. Mol Cell Proteomics 2004; 3(10): 960–9

    Article  PubMed  CAS  Google Scholar 

  133. Unwin RD, Smith DL, Blinco D, et al. Quantitative proteomics reveals posttranslational control as a regulatory factor in primary hematopoietic stem cells. Blood 2006; 107(12): 4687–94

    Article  PubMed  CAS  Google Scholar 

  134. Evans CA, Tonge R, Blinco D, et al. Comparative proteomics of primitive hematopoietic cell populations reveals differences in expression of proteins regulating motility. Blood 2004; 103(10): 3751–9

    Article  PubMed  CAS  Google Scholar 

  135. Ota J, Yamashita Y, Okawa K, et al. Proteomic analysis of hematopoietic stem cell-like fractions in leukemic disorders. Oncogene 2003; 22(36): 5720–8

    Article  PubMed  CAS  Google Scholar 

  136. Zenzmaier C, Kollroser M, Gesslbauer B, et al. Preliminary 2-D chromatographic investigation of the human stem cell proteome. Biochem Biophys Res Commun 2003; 310(2): 483–90

    Article  PubMed  CAS  Google Scholar 

  137. Tao W, Wang M, Voss ED, et al. Comparative proteomic analysis of human CD34+ stem/progenitor cells and mature CD15+ myeloid cells. Stem Cells 2004; 22(6): 1003–14

    Article  PubMed  CAS  Google Scholar 

  138. Zenzmaier C, Gesslbauer B, Grobuschek N, et al. Proteomic profiling of human stem cells derived from umbilical cord blood. Biochem Biophys Res Commun 2005; 328(4): 968–72

    Article  PubMed  CAS  Google Scholar 

  139. Liu F, Lu J, Fan HH, et al. Insights into human CD34+ hematopoietic stem/progenitor cells through a systematically proteomic survey coupled with transcriptome. Proteomics 2006; 6(9): 2673–92

    Article  PubMed  CAS  Google Scholar 

  140. Feldmann RE Jr, Bieback K, Maurer MH, et al. Stem cell proteomes: a profile of human mesenchymal stem cells derived from umbilical cord blood. Electrophoresis 2005; 26(14): 2749–58

    Article  PubMed  CAS  Google Scholar 

  141. Jeong JA, Lee Y, Lee W, et al. Proteomic analysis of the hydrophobic fraction of mesenchymal stem cells derived from human umbilical cord blood. Mol Cells 2006; 22(1): 36–43

    PubMed  CAS  Google Scholar 

  142. vander Kooy D, Weiss S. Why stem cells? Science 2000; 287(5457): 1439–41

    Article  PubMed  Google Scholar 

  143. Daley GQ, Goodell MA, Snyder EY. Realistic prospects for stem cell therapeutics. Hematology Am Soc Hematol Educ Program 2003: 398-418

  144. Chien KR. Stem cells: lost in translation. Nature 2004; 428(6983): 607–8

    Article  PubMed  CAS  Google Scholar 

  145. Rosenzweig A. Cardiac cell therapy: mixed results from mixed cells. N Engl J Med 2006; 355(12): 1274–7

    Article  PubMed  CAS  Google Scholar 

  146. Lunde K, Solheim S, Aakhus S, et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med 2006; 355(12): 1199–209

    Article  PubMed  CAS  Google Scholar 

  147. Schachinger V, Erbs S, Elsasser A, et al. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med 2006; 355(12): 1210–21

    Article  PubMed  CAS  Google Scholar 

  148. Assmus B, Honold J, Schachinger V, et al. Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med 2006; 355(12): 1222–32

    Article  PubMed  CAS  Google Scholar 

  149. Pelletier JP, Transue S, Snyder EL. Pathogen inactivation techniques. Best Pract Res Clin Haematol 2006; 19(1): 205–42

    Article  PubMed  CAS  Google Scholar 

  150. Klein HG. Pathogen inactivation technology: cleansing the blood supply. J Intern Med 2005; 257(3): 224–37

    Article  PubMed  CAS  Google Scholar 

  151. Anderson L, Anderson NG. High resolution two-dimensional electrophoresis of human plasma proteins. Proc Natl Acad Sci U S A 1977; 74(12): 5421–5

    Article  PubMed  CAS  Google Scholar 

  152. Qian WJ, Jacobs JM, Liu T, et al. Advances and challenges in liquid chromatography-mass spectrometry based proteomic profiling for clinical applications. Mol Cell Proteomics 2006; 5(10): 1727–44

    Article  PubMed  CAS  Google Scholar 

  153. Omenn GS. Exploring the human plasma proteome. Proteomics 2005; 5(13): 3223; 3225

    Google Scholar 

  154. Hortin GL. The MALDI-TOF mass spectrometric view of the plasma proteome and peptidome. Clin Chem 2006; 52(7): 1223–37

    Article  PubMed  CAS  Google Scholar 

  155. Adkins JN, Varnum SM, Auberry KJ, et al. Toward a human blood serum proteome: analysis by multidimensional separation coupled with mass spectrometry. Mol Cell Proteomics 2002; 1(12): 947–55

    Article  PubMed  CAS  Google Scholar 

  156. Omenn GS, States DJ, Adamski M, et al. Overview of the HUPO Plasma Proteome Project: results from the pilot phase with 35 collaborating laboratories and multiple analytical groups, generating a core dataset of 3020 proteins and a publicly-available database. Proteomics 2005; 5(13): 3226–45

    Article  PubMed  CAS  Google Scholar 

  157. Tissot JD, Hochstrasser DF, Schneider B, et al. No evidence for protein modifications in fresh frozen plasma after photochemical treatment: an analysis by high-resolution two-dimensional electrophoresis. Br J Haematol 1994; 86(1): 143–6

    Article  PubMed  CAS  Google Scholar 

  158. Crettaz D, Sensebe L, Vu DH, et al. Proteomics of methylene blue photo-treated plasma before and after removal of the dye by an absorbent filter. Proteomics 2004; 4(3): 881–91

    Article  PubMed  CAS  Google Scholar 

  159. Green D. The management of acquired haemophilia. Haemophilia 2006; 12 Suppl. 5: 32–6

    Article  Google Scholar 

  160. Wiedermann CJ, Hoffmann JN, Juers M, et al. High-dose antithrombin III in the treatment of severe sepsis in patients with a high risk of death: efficacy and safety. Crit Care Med 2006; 34(2): 285–92

    Article  PubMed  CAS  Google Scholar 

  161. Kienast J, Juers M, Wiedermann CJ, et al. Treatment effects of high-dose antithrombin without concomitant heparin in patients with severe sepsis with or without disseminated intravascular coagulation. J Thromb Haemost 2006; 4(1): 90–7

    Article  PubMed  CAS  Google Scholar 

  162. Halbmayer WM. Rational, high quality laboratory monitoring before, during, and after infusion of prothrombin complex concentrates. Thromb Res 1999; 95(4 Suppl. 1): S25–30

    Article  PubMed  CAS  Google Scholar 

  163. Josephson CD, Abshire TC. Clinical uses of plasma and plasma fractions: plasma-derived products for hemophilias A and B, and for von Willebrand disease. Best Pract Res Clin Haematol 2006; 19(1): 35–49

    Article  PubMed  CAS  Google Scholar 

  164. Josic D, Hoffer L, Buchacher A, et al. Manufacturing of a prothrombin complex concentrate aiming at low thrombogenicity. Thromb Res 2000; 100(5): 433–41

    Article  PubMed  CAS  Google Scholar 

  165. Brigulla M, Thiele T, Scharf C, et al. Proteomics as a tool for assessment of therapeutics in transfusion medicine: evaluation of prothrombin complex concentrates. Transfusion 2006; 46(3): 377–85

    Article  PubMed  CAS  Google Scholar 

  166. Kohler M, Hellstern P, Lechler E, et al. Thromboembolic complications associated with the use of prothrombin complex and factor IX concentrates. Thromb Haemost 1998; 80(3): 399–402

    PubMed  CAS  Google Scholar 

  167. Eis-Hubinger AM, Sasowski U, Brackmann HH, et al. Parvovirus B19 DNA is frequently present in recombinant coagulation factor VIII products [letter]. Thromb Haemost 1996; 76(6): 1120

    PubMed  CAS  Google Scholar 

  168. Azzi A, DeSantis R, Morfini M, et al. TT virus contaminates first-generation recombinant factor VIII concentrates. Blood 2001; 98(8): 2571–3

    Article  PubMed  CAS  Google Scholar 

  169. Kreil TR, Zimmermann K, Pable S, et al. TT virus does not contaminate first-generation recombinant factor VIII concentrate. Blood2002; 100(6): 2271–2; author reply 2

    Article  PubMed  CAS  Google Scholar 

  170. Ephrem A, Misra N, Hassan G, et al. Immunomodulation of autoimmune and inflammatory diseases with intravenous immunoglobulin. Clin Exp Med 2005; 5(4): 135–40

    Article  PubMed  CAS  Google Scholar 

  171. Bayary J, Dasgupta S, Misra N, et al. Intravenous immunoglobulin in autoimmune disorders: an insight into the immunoregulatory mechanisms. Int Immunopharmacol 2006; 6(4): 528–34

    Article  PubMed  CAS  Google Scholar 

  172. Wittek R. Vaccinia immune globulin: current policies, preparedness, and product safety and efficacy. Int J Infect Dis 2006; 10(3): 193–201

    Article  PubMed  Google Scholar 

  173. Tissot JD, Vu DH, Aubert V, et al. The immunoglobulinopathies: from physiopathology to diagnosis. Proteomics 2002; 2(7): 813–24

    Article  PubMed  CAS  Google Scholar 

  174. Goldfarb MF. Two-dimensional electrophoretic analysis of immunoglobulin patterns in monoclonal gammopathies. Electrophoresis 1992; 13(7): 440–4

    Article  PubMed  CAS  Google Scholar 

  175. Tissot JD, Schneider P, Hohlfeld P, et al. Two-dimensional electrophoresis as an aid in the analysis of the clonality of immunoglobulins. Electrophoresis 1993; 14(12): 1366–71

    Article  PubMed  CAS  Google Scholar 

  176. Dammacco F, Sansonno D, Piccoli C, et al. The cryoglobulins: an overview. Eur J Clin Invest 2001; 31(7): 628–38

    Article  PubMed  CAS  Google Scholar 

  177. Tissot JD, Schifferli JA, Hochstrasser DF, et al. Two-dimensional polyacrylamide gel electrophoresis analysis of cryoglobulins and identification of an IgM-associated peptide. J Immunol Methods 1994; 173(1): 63–75

    Article  PubMed  CAS  Google Scholar 

  178. Damoc E, Youhnovski N, Crettaz D, et al. High resolution proteome analysis of cryoglobulins using Fourier transform-ion cyclotron resonance mass spectrometry. Proteomics 2003; 3(8): 1425–33

    Article  PubMed  CAS  Google Scholar 

  179. Robert D, Barelli S, Crettaz D, et al. Clinical proteomics: study of a cryogel. Proteomics 2006; 6(13): 3958–60

    Article  PubMed  CAS  Google Scholar 

  180. Hermeling S, Crommelin DJ, Schellekens H, et al. Structure-immunogenicity relationships of therapeutic proteins. Pharm Res 2004; 21(6): 897–903

    Article  PubMed  CAS  Google Scholar 

  181. Schellekens H. Factors influencing the immunogenicity of therapeutic proteins. Nephrol Dial Transplant 2005; 20Suppl. 6: vi3–9

    Article  PubMed  CAS  Google Scholar 

  182. Schellekens H, Casadevall N. Immunogenicity of recombinant human proteins: causes and consequences. J Neurol 2004; 251Suppl. 2: II4–9

    PubMed  Google Scholar 

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Acknowledgments

Financial support for the work in the Institut für Immunologie and Transfusionsmedizin and the Institut für Genetik und Funktionelle Genomforschung was provided by the Bundesministerium für Bildung and Forschung (ZIK-FunGene and BMBF/NBL3 reference 01-ZZ0403) and the Landesförderung-sprogramm Mecklenburg Vorpommern (EFRE).

The authors have no conflicts of interest that are directly related to the content of this review.

None of the authors had any conflict of interest directly related to the content of this review.

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  1. Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University, Sauerbruchstraße 17489, Greifswald, Germany

    Thomas Thiele &  Andreas Greinacher

  2. Interfaculty Institute of Genetics and Functional Genomics, Ernst-Moritz-Arndt University, Greifswald, Germany

    Leif Steil & Uwe Völker

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  1. Thomas Thiele
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Correspondence to Andreas Greinacher.

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Thiele, T., Steil, L., Völker, U. et al. Proteomics of Blood-Based Therapeutics. BioDrugs 21, 179–193 (2007). https://doi.org/10.2165/00063030-200721030-00005

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