Biochemical and cell biological changes during platelet activation  Page description

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Details of project

  
Identifier
49392
Type K
Principal investigator Kappelmayer, János
Title in Hungarian Thrombocyta aktiváció során bekövetkező változások biokémiai és sejtbiológiai jellemzés
Title in English Biochemical and cell biological changes during platelet activation
Panel Cellular and Developmental Biology
Department or equivalent Department of Laboratory Medicine (University of Debrecen)
Participants Erdődi, Ferenc
Miszti-Blasius, Kornél
Nagy, Béla
Udvardy, Miklós
Starting date 2005-01-01
Closing date 2008-12-31
Funding (in million HUF) 11.700
FTE (full time equivalent) 5.96
state closed project





 

Final report

  
Results in Hungarian
Ex vivo mintákon végzett analízisek közül elvégeztük 30 db stent beültett beteg esetében perifáriás vérminták analízisét az alábbi thrombocyta aktivációs markerekre: thrombocyta P-selectin, solubilis P-selectin, CD63 expresszió, heterotipikus aggregátumok aránya, mikropartikula mennyiség. Fenti eredményeket korreláltattuk a betegek előzetes kezelési protokolljával (csak ASA, vagy ASA+clopidogrel). A XIII-as faktorral (F XIII) kapcsolatos vizsgálatok során megállapítást nyert, hogy thrombocyták TRAP aktiválása, az FXIII expresszió fokozódásával jár. Azonban kimutattuk, hogy ez a plazmában lévő FXIII kötődése és nem az intracellluláris FXIII felszíni megjelenése miatt jön létre. Specifikus fibrinogének felhasználásával tisztáztuk az FXIII kötődés biokémiai jellemzőit. A thrombocyta foszfatáz inhibitorokkal végzett kísérletek során PRP-ben bizonyítottuk, hogy az 1 és 2A típusú foszfatázoknak csak együttes gátlása hozza létre a thrombocyta aktiválás során észlelhető hatást. TRAP aktivált mintákon bizonyítottuk, hogy mind az aggregáció, mind a P-selectin expresszió dózisfüggő módon gátlódik calyculin (CLA) hatására. Ugyanakkor nem aktivált mintákon azt találtuk, hogy a CLA dózisfüggő módon alakváltozást hoz létre a thrombocytákban, mely aggregometriával, valamint áramlási citometriai fényszórási és antigén expressziós vizsgálatokkal bizonyítható volt.
Results in English
On ex vivo samples we examined 30 cases of stent implanted patients where in peripheral blood samples the following platelet activation markers were investigated: paletelt P-selectin, soluble P-selectin, CD63, heterotypic aggregates, microparticles. The above data were correlated with previous treatment protocol of the patients (ASA only or ASA and clopidogrel). Regarding studies with factor XIII we identified that in TRAP-activated platelets FXIII is elevated on the platelet surface. However, we proved, that FXIII is not derived from intracellular source but is attached from the plasma. By using specific fibrinogens we identified the biochemical requirements for FXIII binding to platelets. The manuscript was submitted to Thrombosis and Haemostasis where a minor revision was required. Regarding phosphatase inhibitors we found that phosphatase 1 and 2A types are both involved in platelet activation, since their simultaneous inhibition by calyculin is required to prevent TRAP-elicited P-selectin axpression and platelet aggregation. At the same time on non-activated platelet samples we found that calyculin dose-dependently inhibited platelet shape-change as measured by aggregometry and flow cytometry.
Full text http://real.mtak.hu/1965/
Decision
Yes





 

List of publications

  
Ratei R, Wolf-Dieter L, Lacombe F, del Poeta G, Kraan J, Gratama J, Kappelmayer J, Karawajew L, Jagoda K, Bjorklund L, de Santiago M, Orao A: Normal Lymphocytes from Leukemic Samples as an Internal Quality Control for Fluorescensce Intensity in Immunophenotyping of Acute Leukemias, Cytometry B Clin Cytometry 70: 173-82, 2006
Ratei R, McDonald A, Lacombe F, Karaevjew L, Jagoda K, Kappelmayer J, Orfao A, Bjorklund L, Gratama J: Discriminant Function Analysis as Decision Support System for the Diagnosis of Acute Leukemia with a Minimal Four Color Screening Panel and Multiparameter Flow Cytometry, Leukemia 92: 698-701, 2007
Miszti-Blasius K, Veszprémi A, Xia L, McEver RP, Kappelmayer J: Lack of P-selectin Glycoprotein Ligand-1 protects mice from thrombosis after thrombotic challenges, Journal of Thrombosis and Haemostasis, 3: Suppl 1, 2005
Végh J, Szodoray P, Kappelmayer J, Csípő I, Udvardy M, Lakos G, Aleksza M, Soltész P, Szilágyi A, Zeher M, Szegedi G, Bodolay E: Clinical and immunological characteristics of mixed connective tissue disease (MCTD) associated with pulmonary arterial hypertonsis, Scandinavian Journal of Immunology 64 (1): 69-76, 2006
Katona K, Herczeg P, Kappelmayer J, Fésüs L, Aradi J: Deoxy-adenozin monophosphate (dAMP) dibutylester induces apoptosis by increasing the dATP level in HL-60 cells, Cancer Letters 235: 281-290, 2006
Rőszer T, Kappelmayer J, Nagy G, Szentmiklosi J, Basnakian A, Banfalvi G: The neuropeptide FMRFamide can protect cells aganist apoptosis in the snail digestive gland, Apoptosis 11 (2): 173-82, 2006
Szabo I, Kappelmayer J, Alekseev SI, Ziskin MC: Millimeter wave induced revesible externalization of phosphatidylserine molecules in cells exposed in vitro, Bioelectromagnetics. 27: 233-244, 2006
Bene L, Kanyári Zs, Bodnár A, Kappelmayer J, Waldmann TA, Vámosi Gy, Damjanovich L: Colorectal carcinoma rearranges cell surface topology and density in CD4+ T cells, Biochem Biophys Research Communications 361: 202-207, 2007
Bárdi E, Bobok I, V Oláh A, Kappelmayer J, Kiss C: Anthracycline antibiotics induce acute renal tubular toxicity in children with cancer, Pathology and Oncology Research 13(3):249-253, 2007
Nagy B Jr, Hevessy Zs, Katona E, Polgar J, Kappelmayer J: Comperative evaluation of FXIIIA and P-selectin expression on the surface of thrombin-activated platelets and microparticles, Journal of Thrombosis and Haemostasis 3: Suppl 1, 2005
Kiss F, Buslig J, Szegedi I, Scholtz B, Kappelmayer J, Kiss C.: Early relapse after rituximab chemoimmuntherapy., Pediatric Blood and Cancer 50:372-375, 2008
Kerekes G, Szekanecz Z, Der H, Sandor Z, Lakos G, Muszbek L, Csipo I, Sipka S, Seres I, Paragh G, Kappelmayer J, Szomják E, Veres K, Szegedi G, Shoenfeld Y, Soltész P.: Endothelial dysfunction and atherosclerosis in rheumatoid arthritis: a munltiparametric analysis using imaging techniques and laboratory markers of inflammation and autoimmunity., Journal of Rheumatology 35: 398-406, 2008
Boda Z, Udvardy M, Rázsó K, Farkas K, Tóth J, Jámbor L, Soltész P, Oláh Zs, Ilonczai P, Szarvas M, Hunyadi J, Sipos T, Litauszky K, Kappelmayer J, Veréb Z, Rajnavölgyi E.: Autologous bone marrow-derived stem cell transplantation in patients with severe peripheral arterial disorders., Clinical and Applied Thrombosis and Haemostasis (in press), 2008
Mohás M, Szigeti N, Markó L, Molnár GA, Cseh J, Laczy B, Tamaskó M, Balla J, Kappelmayer J, Wagner L, Wagner Z, Csiky B, Nagy J, Wittmann I.: Serum total LDH activity and LDH-2 isozyme in nephrotic syndrome., Kidney and Bood Pressure Research 31: 47-54, 2008
Kiss F, Simon A, Csathy L, Hevessy Z, Katona E, Kiss C, Kappelmayer J: A coagulation factor becomes useful in the study of acute leukemias: studies with blood coagulation factor XIII, Cytometry A 73:194-201, 2008
Miner J, Xia L, Yago T, Kappelmayer J, Liu X, Klopocki AG, Shao B, McDaniel M, Setiadi H, Schmidtke D, McEver RP.: Separable requirements for cytoplasmic domain of PSGL-1 in leukocyte rolling and signaling under flow., Blood 112 (5): 2035-2045, 2008
Zold E, Szodoray P, Gaal J, Kappelmayer J, Csathy L, Gyimesi E, Zeher M, Szegedi G, Bodolay E.: Vitamin D in undifferentiated connective tissue disease., Allergy 63: 660-660. Suppl. 88, 2008
Nagy B, Simon Zs, Bagoly Zs, Muszbek L, Kappelmayer J.: Binding of plasma factor XIII to thrombin-receptor activated human platelets., Thrombosis and Hemostasis (in press), 2009
Losonczy G, Rosenberg N, Boda Z, Vereb G, Kappelmayer J, Hauschner H, Bereczky Z, Muszbek L: Three novel mutations in the glycoprotein IIb gene in a patient with type II Glanzmann thrombasthenia, Haematologica/The Hematology 92: 704-707, 2007
Kappelmayer J, Udvardy M, Antal-Szalmás P: Pgp and FLT3: identification and modulation of two proteins that lead to chemotherapy resistance in acute myeloid leukemia, Current Medicinal Chemistry 14: 519-530, 2007
Nagy B Jr, Csongrádi É, Bhattoa HP, Balogh I , Blaskó G, Paragh G, Kappelmayer J, Káplár M: Investigation of Thr715Pro P-selectin gene polymorphism and soluble P-selectin levels in type 2 diabetes mellitus, Thrombosis and Haemostasis 98: 186-191, 2007
Szük T, Nagy B Jr, Bereczky Z, Köszegi Z, Édes I, Kappelmayer J: Effects of ''ad hoc'' clopidogrel loading versus pre-treatment on P-selectin expression after coronary stent implantation, Platelets. 17: 344-346, 2006
Kiss F, Hevessy Z, Veszprémi A, Katona É, Vereb G, Kiss C, Muszbek L, Kappelmayer J: Leukemic lymphoblasts: a novel expression site for coagulation factor XIII subunit A, Thrombosis and Haemostasis 96: 176-182, 2006
Kappelmayer J, Simon Á, Katona É, Szanto A, Nagy L, Kiss A, Kiss Cs: Coagulation factor XIII-A, A flow cytometric intracellular marker in the classification of acute myeloid leukemias, Thrombosis and Haemostasis, 94: 454-9, 2005



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