CalDAG-GEFI deficiency protects mice from FcγRIIa-mediated thrombotic thrombocytopenia induced by CD40L and β2GPI immune complexes

Journal of Thrombosis and Haemostasis

Volumn 12, Issue 12, 2014, Pages 2113-2119

  Amirkhosravi, A ^a   Boulaftali, Y ^b   Robles Carrillo, L ^a   Meyer, T ^a   Mckenzie, S E ^c   Francis, J L ^a   Bergmeier, W ^b  

^a FLORIDA HOSPITAL   (United States)

^b UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^c THOMAS JEFFERSON UNIVERSITY   (United States)

Author keywords

Antigen antibody complex; IgG; Platelet activation; Receptors; Thrombocytopenia; Thrombosis

Indexed keywords

BETA2 GLYCOPROTEIN 1; CALDAG GEFI PROTEIN; CD40 LIGAND; CLOPIDOGREL; FC RECEPTOR IIA; GUANINE NUCLEOTIDE EXCHANGE FACTOR; PADGEM PROTEIN; PURINERGIC P2Y12 RECEPTOR; RAP1 PROTEIN; UNCLASSIFIED DRUG; DIACYLGLYCEROL; P2RY12 PROTEIN, MOUSE; RASGRP2 PROTEIN, MOUSE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIGEN ANTIBODY COMPLEX; ARTICLE; CONTROLLED STUDY; CORE TEMPERATURE; HISTOLOGY; IN VITRO STUDY; MOUSE; NONHUMAN; SHOCK; THROMBOCYTE ACTIVATION; THROMBOCYTE COUNT; THROMBOTIC THROMBOCYTOPENIC PURPURA; ANIMAL; BODY TEMPERATURE; CHEMISTRY; DEFICIENCY; GENETICS; LUNG; METABOLISM; THROMBOCYTE; THROMBOCYTOPENIA; THROMBOSIS; TRANSGENIC MOUSE;

ANIMALS; BETA 2-GLYCOPROTEIN I; BLOOD PLATELETS; BODY TEMPERATURE; CD40 LIGAND; DIGLYCERIDES; GUANINE NUCLEOTIDE EXCHANGE FACTORS; LUNG; MICE; MICE, TRANSGENIC; RAP1 GTP-BINDING PROTEINS; RECEPTORS, PURINERGIC P2Y12; THROMBOCYTOPENIA; THROMBOSIS;

EID: 84916608072     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/jth.12748     Document Type: Article

References (22)

1. Amiral J, Bridey F, Dreyfus M, Vissoc AM, Fressinaud E, Wolf M, Meyer D. Platelet factor 4 complexed to heparin is the target for antibodies generated in heparin-induced thrombocytopenia. Thromb Haemost 1992; 68: 95-6.
2. Warkentin TE, Sheppard JI. Generation of platelet-derived microparticles and procoagulant activity by heparin-induced thrombocytopenia IgG/serum and other IgG platelet agonists: a comparison with standard platelet agonists. Platelets 1999; 10: 319-26.
3. Yin H, Stojanovic-Terpo A, Xu W, Corken A, Zakharov A, Qian F, Pavlovic S, Krbanjevic A, Lyubimov AV, Wang ZJ, Ware J, Du X. Role for platelet glycoprotein Ib-IX and effects of its inhibition in endotoxemia-induced thrombosis, thrombocytopenia, and mortality. Arterioscler Thromb Vasc Biol 2013; 33: 2529-37.
4. Chong BH, Brighton TC, Chesterman CN. Antiphospholipid antibodies and platelets. Semin Thromb Hemost 1995; 21: 76-84.
5. Espinosa G, Cervera R, Font J, Shoenfeld Y. Antiphospholipid syndrome: pathogenic mechanisms. Autoimmun Rev 2003; 2: 86-93.
6. Nalluri SR, Chu D, Keresztes R, Zhu X, Wu S. Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA 2008; 300: 2277-85.
7. Sidiropoulos PI, Boumpas DT. Lessons learned from anti-CD40L treatment in systemic lupus erythematosus patients. Lupus 2004; 13: 391-7.
8. Rosenfeld SI, Looney RJ, Leddy JP, Phipps DC, Abraham GN, Anderson CL. Humanplatelet Fc receptor for immunoglobulin G. Identification as a 40, 000-molecular-weight membrane protein shared by monocytes. J Clin Invest 1985; 76: 2317-22.
9. Mócsai A, Ruland J, Tybulewicz VL. The SYK tyrosine kinase: a crucial player in diverse biological functions. Nat Rev Immunol 2010; 10: 387-402.
10. Stefanini L, Roden RC, Bergmeier W. CalDAG-GEFI is at the nexus of calcium-dependent platelet activation. Blood 2009; 114: 2506-14.
11. Stolla M, Stefanini L, André P, Ouellette TD, Reilly MP, McKenzie SE, Bergmeier W. CalDAG-GEFI deficiency protects mice in a novel model of Fcγ RIIA-mediated thrombosis and thrombocytopenia. Blood 2011; 118: 1113-20.
12. Robles-Carrillo L, Meyer T, Hatfield M, Desai H, Dávila M, Langer F, Amaya M, Garber E, Francis JL, Hsu YM, Amirkhosravi A. Anti-CD40L immune complexes potently activate platelets in vitro and cause thrombosis in FCGR2A transgenic mice. J Immunol 2010; 185: 1577-83.
13. Amirkhosravi A, Meyer T, Robles-Carrillo L, Hatfield M, Desai H, Amaya M, Langer F, McKenzie SE, Francis JL. β2-Glycoprotein 1 antibodies directly activate the platelet IgG receptor, FcRIIa, and cause thrombosis in FCGR2A transgenic but not in wild type mice. Blood 2012; 120: Abstract-106.
14. McKenzie SE, Taylor SM, Malladi P, Yuhan H, Cassel DL, Chien P, Schwartz E, Schreiber AD, Surrey S, Reilly MP. The role of the human Fc receptor Fc gamma RIIA in the immune clearance of platelets: a transgenic mouse model. J Immunol 1999; 162: 4311-8.
15. Meyer T, Robles-Carrillo L, Robson T, Langer F, Desai H, Davila M, Amaya M, Francis JL, Amirkhosravi A. Bevacizumab immune complexes activate platelets and induce thrombosis in FCGR2A transgenic mice. J Thromb Haemost 2009; 7: 171-81.
16. Crittenden JR, Bergmeier W, Zhang Y, Piffath CL, Liang Y, Wagner DD, Housman DE, Graybiel AM. CalDAG-GEFI integrates signaling for platelet aggregation and thrombus formation. Nat Med 2004; 10: 982-6.
17. Polgár J, Eichler P, Greinacher A, Clemetson KJ. Adenosine diphosphate (ADP) and ADP receptor play a major role in platelet activation/aggregation induced by sera from heparin-induced thrombocytopenia patients. Blood 1998; 91: 549-54.
18. Denomme GA. The platelet Fc Receptor in Heparin-induced thrombocytopenia. In: Warkentin TE, Greinacher A, eds. Heparin-Induced Thrombocytopenia, edn, Revised and Expanded. Marcel Dekker, Inc, 2004: 223-50.
19. Stefanini L, Boulaftali Y, Ouellette TD, Holinstat M, Désiré L, Leblond B, Andre P, Conley PB, Bergmeier W. Rap1-Rac1 circuits potentiate platelet activation. Arterioscler Thromb Vasc Biol 2012; 32: 434-41.
20. Bergmeier W, Stefanini L. Platelet ITAM signaling. Curr Opin Hematol 2013; 20: 445-50.
21. Stolla M, Stefanini L, Roden RC, Chavez M, Hirsch J, Greene T, Ouellette TD, Maloney SF, Diamond SL, Poncz M, Woulfe DS, Bergmeier W. The kinetics of αIIbβ3 activation determines the size and stability of thrombi in mice: implications for antiplatelet therapy. Blood 2011; 117: 1005-13.
22. Bergmeier W, Schulte V, Brockhoff G, Bier U, Zirngibl H, Nieswandt B. Flow cytometric detection of activated mouse integrin αIIbβ3 with a novel monoclonal antibody. Cytometry 2002; 48: 80-6.