Platelet proteomics in transfusion medicine: a reality with a challenging but promising future.

摘要: Dear Sir, Platelet proteomics is a young field that took off at the beginning of this century and soon yielded relevant results. The basic concept for platelet proteomic researchers that, because platelets do not have nucleus, an ideal tool to approach their biochemistry. This proved be true thus, during last ten years allowed discovery new receptors signaling proteins, some which were shown play significant role in activation. Indeed, these proteins are being studied as potential anti-thrombotic drug targets1. initial success was taken with cautious optimism by researchers, whom challenge applying more clinical orientated studies. aim take advantage technology environment order find novel biomarkers targets those pathologies where unwanted activation plays role. One fields has productive results transfusion medicine. storage critical importance today’s practice. Platelet concentrates (PLCs) obtained, either apheresis or pooled buffy coats, administered routinely life-saving procedures surgery chemotherapy patients low numbers who function impaired2,3. problem PLCs short shelf life when stored 22 °C, may lead deterioration functionality, condition known lesion. Even though improvements materials lengthened time PCs, it still restricted 5 days risk bacterial infection3. In contrast other blood products, can longer periods using colder temperatures (e.g. erythrocyte plasma), can’t preserved cold conditions they undergo intense modifications shape functionality. These limitations create constant shortage services. Platelet aims help understand altered morphological, biochemical functional features constitute phenomenon By filling gap knowledge, will improve understanding loss design strategies methods enhance our ability maintain optimal time. During combination two-dimensional gel electrophoresis (2-DE)- mass spectrometry (MS)-based approaches been used profile alterations storage. Back 2007, Thiele coworkers differential in-gel (2D-DIGE) MS assess effects on global proteome therapeutic PCs identify could sensitive markers related changes2. Their showed remains quite stable first 5–9 storage, fact, 97% cytosolic didn’t suffer any day 9. Major occurred between 9 15 changes most likely caused degradation2. Proteins detected change remaining 3% after included septin-2, gelsolin β-actin. Interestingly septin 2 affected apoptosis, indicating apoptosis impact Moreover, also study - authors recognize suffers from one important 2-DE-based proteomics, under-representation membrane due high hydrophobicity. To overcome limitation, comprehensively analyze suffered Thon co-workers performed multi-technique over 7-day period3. combined protein-centric (2-DE/DIGE) peptide-centric techniques (isotope-coded affinity tagging, ICAT; isotope tagging relative absolute quantitation, iTRAQ) total 503 differentially expressed proteins. More precisely, 93 identified 2-DE /DIGE, 355 iTRAQ, 139 ICAT. Comparative analysis 2-DE/DIGE, ICAT indicated only five common all three employed3. There overlap among studies, especially same orientation (peptide- protein-centric). They collaborators2 (septin-2, gelsolin, β-actin), further consolidate them possible happening PLCs. Other protein changes, like ones seen talin, 14-3-3, tubulin thrombospondin, excellent agreement two Nevertheless, there disagreements, might differences instrumentation, variations protocols laboratory-to-laboratory, undiscovered post-translational modifications, lack specific detection abundance.4 Platelets produce prothrombotic pro-inflammatory mediators implicated adverse reactions. Correspondingly, central players pathological including cardiovascular disease, major cause death diabetics. view this, 2009 Springer MS-based analyzed diabetic healthy donors 5-day period5. 122 up- down-regulated type-2 diabetics non-diabetic controls 117 whose abundances changed period. replicate findings colleagues2 seeing actin increased colleagues characterize before transfusion. formulate hypotheses experimentation outcomes targeting “high platelets” render less effective even unsafe. In conclusion, application address clinically issues medicine already promising reality. Obviously, many challenges ahead should addressed we standardized introduced method/s choice robust, reproducible, relatively rapid. Multi-center studies bring light into but no doubt future its beginning.