Genomes and Genes
Affiliation: Harvard Medical School
- Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injuryLi Zhu
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 104:1621-6. 2007..As thrombus formation continues, sema4D is shed from the platelet surface and becomes available to interact with receptors on endothelial cells and monocytes, as well as continuing to interact with platelets...
- CalDAG-GEFI and protein kinase C represent alternative pathways leading to activation of integrin alphaIIbbeta3 in plateletsStephen M Cifuni
Immune Disease Institute, Harvard Medical School, Boston, MA, USA
Blood 112:1696-703. 2008..In summary, our study identifies CalDAG-GEFI and PKC as independent pathways leading to Rap1 and alphaIIbbeta3 activation in mouse platelets activated through the PAR4 receptor...
- Mice lacking the signaling molecule CalDAG-GEFI represent a model for leukocyte adhesion deficiency type IIIWolfgang Bergmeier
CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
J Clin Invest 117:1699-707. 2007..Thus, mice engineered to lack CalDAG-GEFI have a combination of defects in leukocyte and platelet functions similar to that of LAD-III patients...
- The role of platelet adhesion receptor GPIbalpha far exceeds that of its main ligand, von Willebrand factor, in arterial thrombosisWolfgang Bergmeier
CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 103:16900-5. 2006..Thus, GPIbalpha contributes to arterial thrombosis by important adhesion mechanisms independent of the binding to VWF...
- Desialylation accelerates platelet clearance after refrigeration and initiates GPIbα metalloproteinase-mediated cleavage in miceA J Gerard Jansen
Translational Medicine Division, Brigham and Women s Hospital, Harvard Medical School, 1 Blackfan Circle, Boston, MA 02115, USA
Blood 119:1263-73. 2012..Desialylation of platelet VWFR therefore triggers platelet clearance and primes GPIbα and GPV for MP-dependent cleavage...
- p38 mitogen-activated protein kinase activation during platelet storage: consequences for platelet recovery and hemostatic function in vivoMatthias Canault
Immune Disease Institute, Boston, MA, USA
Blood 115:1835-42. 2010..In summary, our data suggest that inhibition of p38 MAPK or TACE during storage may significantly improve the quality of stored platelets...
- PSGL-1 regulates platelet P-selectin-mediated endothelial activation and shedding of P-selectin from activated plateletsVandana S Dole
CBR Institute for Biomedical Research, 800 Huntington Avenue, Boston, MA 02115, USA
Thromb Haemost 98:806-12. 2007..The interaction with PSGL-1 also results in rapid shedding of P-selectin thus downregulating the inflammatory potential of the platelet...
- Tumor necrosis factor-alpha-converting enzyme (ADAM17) mediates GPIbalpha shedding from platelets in vitro and in vivoWolfgang Bergmeier
CBR Institute for Biomedical Research, Harvard Medical School, Boston, Mass 02115 6399, USA
Circ Res 95:677-83. 2004..In conclusion, our data demonstrate that TACE is expressed in platelets and that it is the key enzyme mediating shedding of GPIbalpha...
- Activated platelets induce Weibel-Palade-body secretion and leukocyte rolling in vivo: role of P-selectinVandana S Dole
CBR Institute for Biomedical Research, Boston, MA 02115, USA
Blood 106:2334-9. 2005..We conclude that the presence of activated platelets in circulation promotes acute inflammation by stimulating secretion of Weibel-Palade bodies and P-selectin-mediated leukocyte rolling...
- von Willebrand factor and factor VIII are independently required to form stable occlusive thrombi in injured veinsAnil K Chauhan
CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA
Blood 109:2424-9. 2007..Thus, VWF likely uses other adhesion receptors besides GPIbalpha in thrombus growth under venous shear conditions. Our studies document crucial roles for VWF and FVIII in experimental thrombosis under venous flow conditions in vivo...
- In vitro function and phagocytosis of galactosylated platelet concentrates after long-term refrigerationAleksandar M Babic
Department of Pathology, Division of Translational Medicine, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
Transfusion 47:442-51. 2007..PLT-associated galactosyltransferase efficiently galactosylates chilled PLTs in the presence of its substrate UDP-galactose is added to PLT-rich plasma...
- Systemic antithrombotic effects of ADAMTS13Anil K Chauhan
CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
J Exp Med 203:767-76. 2006..Our findings reveal that ADAMTS13 has a powerful natural antithrombotic activity and recombinant ADAMTS13 could be used as an antithrombotic agent...
- Mechanisms and implications of platelet discoid shapeJoseph E Italiano
Division of Hematology and Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
Blood 101:4789-96. 2003..Together, these findings highlight the essential requirements of the MK/platelet-restricted beta1-tubulin isoform in platelet structure and suggest that spherocytosis does not impair many aspects of platelet function...
- Oxidative stress activates ADAM17/TACE and induces its target receptor shedding in platelets in a p38-dependent fashionAlexander Brill
Immune Disease Institute, 3 Blackfan Circle, 3rd Floor, Boston, MA 02115, USA
Cardiovasc Res 84:137-44. 2009..Oxidative stress accompanies inflammatory and vascular diseases. The objective of this study was to explore whether reactive oxygen species can activate shedding of platelet receptors and thus suppress platelet function...
- Interactions between the megakaryocyte/platelet-specific beta1 tubulin and the secretory leukocyte protease inhibitor SLPI suggest a role for regulated proteolysis in platelet functionsHarald Schulze
Dana Farber Cancer Institute, 1 Jimmy Fund Way, Boston, MA 02115, USA
Blood 104:3949-57. 2004..SLPI may thus have unanticipated roles in MK and platelet functions, including regulated proteolysis after activation...
- Metalloproteinase inhibitors improve the recovery and hemostatic function of in vitro-aged or -injured mouse plateletsWolfgang Bergmeier
The CBR Institute for Biomedical Research, Inc, 800 Huntington Ave, Boston, MA 02115, USA
Blood 102:4229-35. 2003..Surface expression of GPIbalpha might be a powerful marker to determine the quality of platelet concentrates, because it reflects metalloproteinase activity in vitro...
- Antithrombotic activity of TNF-alphaBeatrice Cambien
The CBR Institute for Biomedical Research Inc, Boston, Massachusetts 02115, USA
J Clin Invest 112:1589-96. 2003..This effect is not exerted directly on platelets but mediated through the rapid generation of NO in the vessel wall...
- GPVI down-regulation in murine platelets through metalloproteinase-dependent sheddingWolfgang Bergmeier
The Center for Blood Research, Institute for Biomedical Research, Department of Pathology, Harvard Medical School, Boston, Massachusetts, UDA
Thromb Haemost 91:951-8. 2004....
- A direct role for C1 inhibitor in regulation of leukocyte adhesionShenghe Cai
The CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA
J Immunol 174:6462-6. 2005..Direct involvement of C1INH in modulation of selectin-mediated cell adhesion may be an important mechanism in the physiologic suppression of inflammation, and may partially explain its utility in therapy of inflammatory diseases...
- The clearance mechanism of chilled blood plateletsKarin M Hoffmeister
Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
Cell 112:87-97. 2003..Chilled platelets bind vWf and function normally in vitro and ex vivo after transfusion into CR3-deficient mice. Therefore, GPIb modification might permit cold platelet storage...
- R93W mutation in Orai1 causes impaired calcium influx in plateletsWolfgang Bergmeier
Immune Disease Institute and Harvard Medical School, Boston, MA, USA
Blood 113:675-8. 2009..In contrast, these adherent Orai1(R93W) platelets were defective in surface phosphatidylserine exposure, suggesting that Orai1 is crucial for the platelets' procoagulant response rather than for other Ca(2+)-dependent cellular responses...
- Thrombocytopenia and platelet abnormalities in high-density lipoprotein receptor-deficient miceVandana S Dole
Biology Department, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Arterioscler Thromb Vasc Biol 28:1111-6. 2008..Here we examined the influence of SR-BI deficiency on platelets...
- Glycoprotein Ibalpha and von Willebrand factor in primary platelet adhesion and thrombus formation: lessons from mutant miceWolfgang Bergmeier
Cardeza Foundation and Department of Medicine, Thomas Jefferson University, 1015 Walnut Street, Philadelphia, PA 19007, USA
Thromb Haemost 99:264-70. 2008..Recent studies in mutant mice have shed new light on the importance of either molecule for the development of arterial and venous thrombosis. In this review, we summarize the most important aspects from these studies...
- Aspirin induces platelet receptor shedding via ADAM17 (TACE)Barsom Aktas
Rudolf Virchow Center for Experimental Biomedicine, Versbacherstrasse 9, 97078 Wurzburg, Germany
J Biol Chem 280:39716-22. 2005..These data demonstrate that aspirin at high concentrations induces shedding of GPIbalpha and GPV by an ADAM17-dependent mechanism and that this process can occur in vivo...
- CalDAG-GEFI integrates signaling for platelet aggregation and thrombus formationJill R Crittenden
Department of Brain and Cognitive Sciences, and McGovern Institute for Brain Research, Massachusetts Institute of Technology, 45 Carleton Street, E25 618, Cambridge, Massachusetts 02139, USA
Nat Med 10:982-6. 2004..These results suggest that analogous signaling defects are likely to occur in the central nervous system when CalDAG-GEFI is absent or compromised in function...
- Complementary roles of glycoprotein VI and alpha2beta1 integrin in collagen-induced thrombus formation in flowing whole blood ex vivoMarijke J E Kuijpers
Department of Biochemistry, CARIM, Maastricht University, Maastricht, The Netherlands
FASEB J 17:685-7. 2003....
- Regulation of platelet granule exocytosis by S-nitrosylationCraig N Morrell
Department of Comparative Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 102:3782-7. 2005..Platelets lacking endothelial NO synthase show increased rolling on venules, increased thrombosis in arterioles, and increased exocytosis in vivo. Regulation of exocytosis is thus a mechanism by which NO regulates thrombosis...
- Flow-cytometric analysis of mouse platelet functionBernhard Nieswandt
Department of Vascular Biology, Rudolf Virchow Centre for Experimental Biomedicine, University of Wuerzburg, Germany
Methods Mol Biol 272:255-68. 2004
- Effect of infusing rat monoclonal antibodies to the murine GPIb-IX-V complex on platelet and megakaryocyte morphology in miceChristel Poujol
UMR 5533 CNRS, , Pessac, France
Platelets 14:35-45. 2003..These changes continued into the recovery phase. The anti-GPV MoAb had no effect on MK. Thus, anti-platelet antibodies can induce a different medullary response even when binding to the same receptor...
- A critical role of platelet adhesion in the initiation of atherosclerotic lesion formationSteffen Massberg
Deutsches Herzzentrum und 1 Medizinische Klinik, Technische Universitat Munchen, Germany
J Exp Med 196:887-96. 2002..These findings establish the platelet as a major player in initiation of the atherogenetic process...
- Flow cytometric detection of activated mouse integrin alphaIIbbeta3 with a novel monoclonal antibodyWolfgang Bergmeier
Department of Molecular Oncology, General Surgery, Witten/Herdecke University, Wuppertal, Germany
Cytometry 48:80-6. 2002..Furthermore, JON/A(FITC) and JON/A(PE) provide the first examples of fluorescent antibody derivatives with identical antigenic specificity that allow the discrimination between the resting and the activated state of an integrin...