Profiling of alterations in platelet proteins during storage of platelet concentrates
Thomas Thiele
From the Institute for Immunology and Transfusion Medicine; Interfaculty Institute for Genetics and Functional Genomics; Department of Otorhinolaryngology, Head and Neck Surgery, Ernst-Moritz-Arndt University, Greifswald, Germany; and the Theodor Kocher Institute, Universität Bern, Bern, Switzerland.
Search for more papers by this authorLeif Steil
From the Institute for Immunology and Transfusion Medicine; Interfaculty Institute for Genetics and Functional Genomics; Department of Otorhinolaryngology, Head and Neck Surgery, Ernst-Moritz-Arndt University, Greifswald, Germany; and the Theodor Kocher Institute, Universität Bern, Bern, Switzerland.
Search for more papers by this authorSimon Gebhard
From the Institute for Immunology and Transfusion Medicine; Interfaculty Institute for Genetics and Functional Genomics; Department of Otorhinolaryngology, Head and Neck Surgery, Ernst-Moritz-Arndt University, Greifswald, Germany; and the Theodor Kocher Institute, Universität Bern, Bern, Switzerland.
Search for more papers by this authorChristian Scharf
From the Institute for Immunology and Transfusion Medicine; Interfaculty Institute for Genetics and Functional Genomics; Department of Otorhinolaryngology, Head and Neck Surgery, Ernst-Moritz-Arndt University, Greifswald, Germany; and the Theodor Kocher Institute, Universität Bern, Bern, Switzerland.
Search for more papers by this authorElke Hammer
From the Institute for Immunology and Transfusion Medicine; Interfaculty Institute for Genetics and Functional Genomics; Department of Otorhinolaryngology, Head and Neck Surgery, Ernst-Moritz-Arndt University, Greifswald, Germany; and the Theodor Kocher Institute, Universität Bern, Bern, Switzerland.
Search for more papers by this authorMatthias Brigulla
From the Institute for Immunology and Transfusion Medicine; Interfaculty Institute for Genetics and Functional Genomics; Department of Otorhinolaryngology, Head and Neck Surgery, Ernst-Moritz-Arndt University, Greifswald, Germany; and the Theodor Kocher Institute, Universität Bern, Bern, Switzerland.
Search for more papers by this authorNorbert Lubenow
From the Institute for Immunology and Transfusion Medicine; Interfaculty Institute for Genetics and Functional Genomics; Department of Otorhinolaryngology, Head and Neck Surgery, Ernst-Moritz-Arndt University, Greifswald, Germany; and the Theodor Kocher Institute, Universität Bern, Bern, Switzerland.
Search for more papers by this authorKenneth J. Clemetson
From the Institute for Immunology and Transfusion Medicine; Interfaculty Institute for Genetics and Functional Genomics; Department of Otorhinolaryngology, Head and Neck Surgery, Ernst-Moritz-Arndt University, Greifswald, Germany; and the Theodor Kocher Institute, Universität Bern, Bern, Switzerland.
Search for more papers by this authorUwe Völker
From the Institute for Immunology and Transfusion Medicine; Interfaculty Institute for Genetics and Functional Genomics; Department of Otorhinolaryngology, Head and Neck Surgery, Ernst-Moritz-Arndt University, Greifswald, Germany; and the Theodor Kocher Institute, Universität Bern, Bern, Switzerland.
Search for more papers by this authorAndreas Greinacher
From the Institute for Immunology and Transfusion Medicine; Interfaculty Institute for Genetics and Functional Genomics; Department of Otorhinolaryngology, Head and Neck Surgery, Ernst-Moritz-Arndt University, Greifswald, Germany; and the Theodor Kocher Institute, Universität Bern, Bern, Switzerland.
Search for more papers by this authorThomas Thiele
From the Institute for Immunology and Transfusion Medicine; Interfaculty Institute for Genetics and Functional Genomics; Department of Otorhinolaryngology, Head and Neck Surgery, Ernst-Moritz-Arndt University, Greifswald, Germany; and the Theodor Kocher Institute, Universität Bern, Bern, Switzerland.
Search for more papers by this authorLeif Steil
From the Institute for Immunology and Transfusion Medicine; Interfaculty Institute for Genetics and Functional Genomics; Department of Otorhinolaryngology, Head and Neck Surgery, Ernst-Moritz-Arndt University, Greifswald, Germany; and the Theodor Kocher Institute, Universität Bern, Bern, Switzerland.
Search for more papers by this authorSimon Gebhard
From the Institute for Immunology and Transfusion Medicine; Interfaculty Institute for Genetics and Functional Genomics; Department of Otorhinolaryngology, Head and Neck Surgery, Ernst-Moritz-Arndt University, Greifswald, Germany; and the Theodor Kocher Institute, Universität Bern, Bern, Switzerland.
Search for more papers by this authorChristian Scharf
From the Institute for Immunology and Transfusion Medicine; Interfaculty Institute for Genetics and Functional Genomics; Department of Otorhinolaryngology, Head and Neck Surgery, Ernst-Moritz-Arndt University, Greifswald, Germany; and the Theodor Kocher Institute, Universität Bern, Bern, Switzerland.
Search for more papers by this authorElke Hammer
From the Institute for Immunology and Transfusion Medicine; Interfaculty Institute for Genetics and Functional Genomics; Department of Otorhinolaryngology, Head and Neck Surgery, Ernst-Moritz-Arndt University, Greifswald, Germany; and the Theodor Kocher Institute, Universität Bern, Bern, Switzerland.
Search for more papers by this authorMatthias Brigulla
From the Institute for Immunology and Transfusion Medicine; Interfaculty Institute for Genetics and Functional Genomics; Department of Otorhinolaryngology, Head and Neck Surgery, Ernst-Moritz-Arndt University, Greifswald, Germany; and the Theodor Kocher Institute, Universität Bern, Bern, Switzerland.
Search for more papers by this authorNorbert Lubenow
From the Institute for Immunology and Transfusion Medicine; Interfaculty Institute for Genetics and Functional Genomics; Department of Otorhinolaryngology, Head and Neck Surgery, Ernst-Moritz-Arndt University, Greifswald, Germany; and the Theodor Kocher Institute, Universität Bern, Bern, Switzerland.
Search for more papers by this authorKenneth J. Clemetson
From the Institute for Immunology and Transfusion Medicine; Interfaculty Institute for Genetics and Functional Genomics; Department of Otorhinolaryngology, Head and Neck Surgery, Ernst-Moritz-Arndt University, Greifswald, Germany; and the Theodor Kocher Institute, Universität Bern, Bern, Switzerland.
Search for more papers by this authorUwe Völker
From the Institute for Immunology and Transfusion Medicine; Interfaculty Institute for Genetics and Functional Genomics; Department of Otorhinolaryngology, Head and Neck Surgery, Ernst-Moritz-Arndt University, Greifswald, Germany; and the Theodor Kocher Institute, Universität Bern, Bern, Switzerland.
Search for more papers by this authorAndreas Greinacher
From the Institute for Immunology and Transfusion Medicine; Interfaculty Institute for Genetics and Functional Genomics; Department of Otorhinolaryngology, Head and Neck Surgery, Ernst-Moritz-Arndt University, Greifswald, Germany; and the Theodor Kocher Institute, Universität Bern, Bern, Switzerland.
Search for more papers by this authorSupport by the Swiss National Science Foundation, Grant 310000-107754 (KJC); Alfried Krupp Wissenschaftskollegs Greifswald (KJC); BMBF-ZIK-FunGene and BMBF/NBL3 [01-ZZ0403] (UV and AG); Landesförderungsprogramm Mecklenburg Vorpommern (EFRE to AG).
Abstract
BACKGROUND: The quality of platelet concentrates (PCs) is primarily determined in vitro by selective methods (e.g., pH, aggregometry), which provide only limited information on certain platelet (PLT) characteristics. In contrast, proteomic technologies provide a comprehensive overview of the PLT proteome. High interassay variability, however, limits meaningful assessment of samples taken from the same product over time or before and after processing.
STUDY DESIGN AND METHODS: Differential in-gel electrophoresis (DIGE) and mass spectrometry were applied to analyze changes in the PLT proteome during storage of PCs.
RESULTS: DIGE provides a comprehensive and reproducible overview of the cytoplasmic PLT proteome (median standard deviation of protein spot intensities, 5%-9%). Although 97 percent of cytosolic PLT proteins remained unchanged over a 9-day storage period, septin 2 showed characteristic alterations that preceded by several days more widespread alterations affecting numerous other proteins. Also β-actin and gelsolin are potential marker proteins for changes in the PLT proteome. Interestingly septin 2 and gelsolin are affected during apoptosis, indicating that apoptosis in PCs may have an impact on PLT storage.
CONCLUSION: DIGE is a tool for comprehensively assessing the impact of storage on the global proteome profile of therapeutic PCs. Most of the changes detected are in high-abundance PLT proteins.
REFERENCES
- 1 Seghatchian J, Krailadsiri P. The platelet storage lesion. Transfus Med Rev 1997; 11: 130-44.
- 2 Li J, Xia Y, Bertino AM, et al. The mechanism of apoptosis in human platelets during storage. Transfusion 2000; 40: 1320-9.
- 3 Gulliksson H. Defining the optimal storage conditions for the long-term storage of platelets. Transfus Med Rev 2003; 17: 209-15.
- 4 Dale GL. Platelet kinetics. Curr Opin Hematol 1997; 4: 330-4.
- 5 Simonsen AC, Johansson PI, Conlan MG, et al. Transfusion of 7-day-old amotosalen photochemically treated buffy-coat platelets to patients with thrombocytopenia: a pilot study. Transfusion 2006; 46: 424-33.
- 6 Greinacher A, Warkentin TE. Transfusion medicine in the era of genomics and proteomics. Transfus Med Rev 2005; 19: 288-94.
- 7 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: 11-24.
- 8 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: 335-41.
- 9 Garcia BA, Smalley DM, Cho H, et al. The platelet microparticle proteome. J Proteome Res 2005; 4: 1516-21.
- 10 Thadikkaran L, Siegenthaler MA, Crettaz D, et al. Recent advances in blood-related proteomics. Proteomics 2005; 5: 3019-34.
- 11 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: 656-68.
- 12 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: 3193-204.
- 13 Marcus K, Moebius J, Meyer HE. Differential analysis of phosphorylated proteins in resting and thrombin-stimulated human platelets. Anal Bioanal Chem 2003; 376: 973-93.
- 14 Unlu M, Morgan ME, Minden JS. Difference gel electrophoresis: a single gel method for detecting changes in protein extracts. Electrophoresis 1997; 18: 2071-7.
- 15 Kluter H, Dorges L, Maass E, et al. In-vivo evaluation of random donor platelet concentrates from pooled buffy coats. Ann Hematol 1996; 73: 85-9.
- 16 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: 377-85.
- 17 Eymann C, Dreisbach A, Albrecht D, et al. A comprehensive proteome map of growing Bacillus subtilis cells. Proteomics 2004; 4: 2849-76.
- 18 Olsen JV, Ong SE, Mann M. Trypsin cleaves exclusively C-terminal to arginine and lysine residues. Mol Cell Proteomics 2004; 3: 608-14.
- 19 Karp NA, Lilley KS. Maximising sensitivity for detecting changes in protein expression: experimental design using minimal CyDyes. Proteomics 2005; 5: 3105-15.
- 20 Huang YW, Surka MC, Reynaud D, et al. GTP binding and hydrolysis kinetics of human septin 2. FEBS J 2006; 273: 3248-60.
- 21 Trimble WS. Septins: a highly conserved family of membrane-associated GTPases with functions in cell division and beyond. J Membr Biol 1999; 169: 75-81.
- 22 Schmidt K, Nichols BJ. Functional interdependence between septin and actin cytoskeleton. BMC Cell Biol 2004; 5: 43.
- 23 Ostergaard M, Hansen GA, Vorum H, Honore B. Proteomic profiling of fibroblasts reveals a modulating effect of extracellular calumenin on the organization of the actin cytoskeleton. Proteomics 2006; 6: 3509-19.
- 24 Spiliotis ET, Nelson WJ. Here come the septins: novel polymers that coordinate intracellular functions and organization. J Cell Sci 2006; 119: 4-10.
- 25 Shcherbina A, Remold-O'Donnell E. Role of caspase in a subset of human platelet activation responses. Blood 1999; 93: 4222-31.
- 26 Wolf BB, Goldstein JC, Stennicke HR, et al. Calpain functions in a caspase-independent manner to promote apoptosis-like events during platelet activation. Blood 1999; 94: 1683-92.
- 27 Hall PA, Jung K, Hillan KJ, Russell SE. Expression profiling the human septin gene family. J Pathol 2005; 206: 269-78.
- 28 Stephens G, Yan Y, Jandrot-Perrus M, et al. Platelet activation induces metalloproteinase-dependent GP VI cleavage to down-regulate platelet reactivity to collagen. Blood 2005; 105: 186-91.
- 29 Lee AY, Park BC, Jang M, et al. Identification of caspase-3 degradome by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight analysis. Proteomics 2004; 4: 3429-36.
- 30 Amelia Santos M, Marques SM, Tuccinardi T, et al. Design, synthesis and molecular modeling study of iminodiacetyl monohydroxamic acid derivatives as MMP inhibitors. Bioorg Med Chem 2006; 14: 7539-50.
- 31 Washburn MP, Wolters D, Yates JR 3rd. Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat Biotechnol 2001; 19: 242-7.