The Wagner lab studies how blood cells respond to injury or stressful situations and initiate defensive or reparatory processes. Specifically, they investigate the crucial role of cellular adhesion interactions in the response process, as well as the regulation of the adhesion molecules involved in normal physiology and in pathological situations.
Blood cells called platelets form a platelet plug to stop bleeding. Leukocytes (white blood cells) emigrate from the blood vessels to fight invading infectious agents and/or release biological mediators that stimulate the function of the surrounding organ to better respond to the demands of stress. All this requires activation of adhesive processes that allow vascular cells to bind to each other and to cells in the organs where the leukocytes emigrate.
To advance their work, Wagner and colleagues have engineered mice lacking platelet, endothelial, or leukocyte adhesion receptors. These animals permit modeling of human diseases with similar genetic defects and evaluation of the performance of mutant blood cells in live vessels through intravital microscopy. The Wagner lab studies platelet adhesion to the vessel wall, which can lead to thrombus formation and sometimes embolization. Recently, they observed that nuclear DNA ejected by stimulated leukocytes (NETs) greatly enhanced pathological thrombosis and organ injury during inflammation.
Wagner and colleagues also are researching the importance of adhesion molecules in inflammatory processes such as atherosclerosis, the narrowing of arteries. They have observed that leukocytes recruited to the liver help to regulate fat metabolism and help to prevent obesity. The lab began to visualize blood vessels in the brain and study mechanisms involved in the formation of the blood brain barrier, which prevents uncontrolled leakage of molecules from the blood into the central nervous system. They ask, do malfunctions of brain microcirculation contribute to the etiology of neurodegenerative diseases such as Alzheimer's? Using animal models, they are testing new ways to modulate blood brain barrier permeability and to evaluate inhibitors of adhesion molecules as possible agents to prevent heart disease and/or thrombosis.
Research Background
Dr. Wagner received her Diploma of Biochemistry from the Université de Geneve, Switzerland and Ph.D. in Biology from the Massachusetts Institute of Technology. She served on the faculty at the University of Rochester, NY and Tufts University School of Medicine before coming to Harvard Medical School in 1994. She is the Edwin Cohn Professor of Pediatrics, a senior investigator in the Program in Cellular and Molecular Medicine, and a member of the Division of Hematology/Oncology at Boston Children's Hospital.
Publications
Sex-specific NLRP3 activation in neutrophils promotes neutrophil recruitment and NETosis in the murine model of diffuse alveolar hemorrhage. Front Immunol. 2024; 15:1466234. View Abstract
Reflections on Targeting Neutrophil Extracellular Traps in Deep Vein Thrombosis. Arterioscler Thromb Vasc Biol. 2024 08; 44(8):1719-1724. View Abstract
Neutrophil NLRP3 promotes cardiac injury following acute myocardial infarction through IL-1ß production, VWF release and NET deposition in the myocardium. Sci Rep. 2024 06 24; 14(1):14524. View Abstract
Neutrophil peptidylarginine deiminase 4 plays a systemic role in obesity-induced chronic inflammation in mice. J Thromb Haemost. 2024 May; 22(5):1496-1509. View Abstract
NLRP3 is essential for neutrophil polarization and chemotaxis in response to leukotriene B4 gradient. Proc Natl Acad Sci U S A. 2023 08 29; 120(35):e2303814120. View Abstract
Inhibition of protein arginine deiminase 4 prevents inflammation-mediated heart failure in arthritis. Life Sci Alliance. 2023 10; 6(10). View Abstract
Alleviation of arthritis through prevention of neutrophil extracellular traps by an orally available inhibitor of protein arginine deiminase 4. Sci Rep. 2023 02 23; 13(1):3189. View Abstract
NLRP3 inflammasome activation in neutrophils directs early inflammatory response in murine peritonitis. Sci Rep. 2022 Dec 09; 12(1):21313. View Abstract
Anti-inflammatory protective effect of ADAMTS-13 in murine arthritis models. J Thromb Haemost. 2022 Oct; 20(10):2386-2393. View Abstract
Thromboinflammation: From Atherosclerosis to COVID-19. Arterioscler Thromb Vasc Biol. 2022 09; 42(9):1103-1112. View Abstract
The Prominent Role of Hematopoietic Peptidyl Arginine Deiminase 4 in Arthritis: Collagen- and Granulocyte Colony-Stimulating Factor-Induced Arthritis Model in C57BL/6 Mice. Arthritis Rheumatol. 2022 07; 74(7):1139-1146. View Abstract
Neutrophil phenotypes and functions in cancer: A consensus statement. J Exp Med. 2022 06 06; 219(6). View Abstract
Inflammasome activation in neutrophils of patients with severe COVID-19. Blood Adv. 2022 04 12; 6(7):2001-2013. View Abstract
Paul S. Frenette (1965-2021). Cell Stem Cell. 2021 10 07; 28(10):1686-1689. View Abstract
Paul S. Frenette (1965-2021). Dev Cell. 2021 Oct 11; 56(19):2688-2691. View Abstract
Paul S. Frenette (1965-2021). Cell. 2021 Sep 30; 184(20):5073-5076. View Abstract
The role of SERPIN citrullination in thrombosis. Cell Chem Biol. 2021 12 16; 28(12):1728-1739.e5. View Abstract
NLRP3 Inflammasome Assembly in Neutrophils Is Supported by PAD4 and Promotes NETosis Under Sterile Conditions. Front Immunol. 2021; 12:683803. View Abstract
Citrullinated Fibrinogen Renders Clots Mechanically Less Stable, but Lysis-Resistant. Circ Res. 2021 07 09; 129(2):342-344. View Abstract
Neutrophil stimulation with citrullinated histone H4 slows down calcium influx and reduces NET formation compared with native histone H4. PLoS One. 2021; 16(5):e0251726. View Abstract
The role of platelets in thrombus fibrosis and vessel wall remodeling after venous thrombosis. J Thromb Haemost. 2021 02; 19(2):387-399. View Abstract
Reply to Liu: The disassembly of the actin cytoskeleton is an early event during NETosis. Proc Natl Acad Sci U S A. 2020 09 15; 117(37):22655-22656. View Abstract
Cellular Mechanisms of NETosis. Annu Rev Cell Dev Biol. 2020 10 06; 36:191-218. View Abstract
NETosis proceeds by cytoskeleton and endomembrane disassembly and PAD4-mediated chromatin decondensation and nuclear envelope rupture. Proc Natl Acad Sci U S A. 2020 03 31; 117(13):7326-7337. View Abstract
Recombinant human ADAMTS13 treatment and anti-NET strategies enhance skin allograft survival in mice. Am J Transplant. 2020 04; 20(4):1162-1169. View Abstract
Resolvin D4 attenuates the severity of pathological thrombosis in mice. Blood. 2019 10 24; 134(17):1458-1468. View Abstract
Extracellular DNA NET-Works With Dire Consequences for Health. Circ Res. 2019 08 02; 125(4):470-488. View Abstract
Plasma Peptidylarginine Deiminase IV Promotes VWF-Platelet String Formation and Accelerates Thrombosis After Vessel Injury. Circ Res. 2019 08 16; 125(5):507-519. View Abstract
Solid peripheral tumor leads to systemic inflammation, astrocyte activation and signs of behavioral despair in mice. PLoS One. 2018; 13(11):e0207241. View Abstract
Neutrophil cytoplasts induce TH17 differentiation and skew inflammation toward neutrophilia in severe asthma. Sci Immunol. 2018 08 03; 3(26). View Abstract
Peptidylarginine deiminase 4: a nuclear button triggering neutrophil extracellular traps in inflammatory diseases and aging. FASEB J. 2018 Jun 20; fj201800691R. View Abstract
Roles of PAD4 and NETosis in Experimental Atherosclerosis and Arterial Injury: Implications for Superficial Erosion. Circ Res. 2018 06 22; 123(1):33-42. View Abstract
Citrullinated histone H3, a biomarker of neutrophil extracellular trap formation, predicts the risk of venous thromboembolism in cancer patients. J Thromb Haemost. 2018 03; 16(3):508-518. View Abstract
Recombinant Human ADAMTS13 Treatment Improves Myocardial Remodeling and Functionality After Pressure Overload Injury in Mice. J Am Heart Assoc. 2018 01 24; 7(3). View Abstract
Sirt3 deficiency does not affect venous thrombosis or NETosis despite mild elevation of intracellular ROS in platelets and neutrophils in mice. PLoS One. 2017; 12(12):e0188341. View Abstract
A key role for Rac and Pak signaling in neutrophil extracellular traps (NETs) formation defines a new potential therapeutic target. Am J Hematol. 2018 02; 93(2):269-276. View Abstract
Unraveling Vascular Inflammation: From Immunology to Imaging. J Am Coll Cardiol. 2017 Sep 12; 70(11):1403-1412. View Abstract
Mast Cells Granular Contents Are Crucial for Deep Vein Thrombosis in Mice. Circ Res. 2017 Sep 29; 121(8):941-950. View Abstract
ADAMTS13 Deficiency Worsens Colitis and Exogenous ADAMTS13 Administration Decreases Colitis Severity in Mice. TH Open. 2017 Jun; 1(1):e11-e23. View Abstract
PAD4 Deficiency Decreases Inflammation and Susceptibility to Pregnancy Loss in a Mouse Model. Biol Reprod. 2016 12; 95(6):132. View Abstract
Limiting prothrombin activation to meizothrombin is compatible with survival but significantly alters hemostasis in mice. Blood. 2016 08 04; 128(5):721-31. View Abstract
Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease. Science. 2016 Apr 22; 352(6284):463-6. View Abstract
NETosis promotes cancer-associated arterial microthrombosis presenting as ischemic stroke with troponin elevation. Thromb Res. 2016 Mar; 139:56-64. View Abstract
Flow cytometric assay for direct quantification of neutrophil extracellular traps in blood samples. Am J Hematol. 2015 Dec; 90(12):1155-8. View Abstract
Diabetes primes neutrophils to undergo NETosis, which impairs wound healing. Nat Med. 2015 Jul; 21(7):815-9. View Abstract
ADAMTS13 Endopeptidase Protects against Vascular Endothelial Growth Factor Inhibitor-Induced Thrombotic Microangiopathy. J Am Soc Nephrol. 2016 Jan; 27(1):120-31. View Abstract
Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation. Nat Chem Biol. 2015 Mar; 11(3):189-91. View Abstract
PAD4-deficiency does not affect bacteremia in polymicrobial sepsis and ameliorates endotoxemic shock. Blood. 2015 Mar 19; 125(12):1948-56. View Abstract
Dietary omega-3 alpha-linolenic acid does not prevent venous thrombosis in mice. Thromb Haemost. 2015 Jan; 113(1):177-84. View Abstract
Heme-induced neutrophil extracellular traps contribute to the pathogenesis of sickle cell disease. Blood. 2014 Jun 12; 123(24):3818-27. View Abstract
NETosis: a new factor in tumor progression and cancer-associated thrombosis. Semin Thromb Hemost. 2014 Apr; 40(3):277-83. View Abstract
Thrombosis: tangled up in NETs. Blood. 2014 May 01; 123(18):2768-76. View Abstract
VWF-mediated leukocyte recruitment with chromatin decondensation by PAD4 increases myocardial ischemia/reperfusion injury in mice. Blood. 2014 Jan 02; 123(1):141-8. View Abstract
Endothelial Von Willebrand factor promotes blood-brain barrier flexibility and provides protection from hypoxia and seizures in mice. Arterioscler Thromb Vasc Biol. 2013 Sep; 33(9):2112-20. View Abstract
Elevated levels of circulating DNA and chromatin are independently associated with severe coronary atherosclerosis and a prothrombotic state. Arterioscler Thromb Vasc Biol. 2013 Aug; 33(8):2032-2040. View Abstract
Neutrophil histone modification by peptidylarginine deiminase 4 is critical for deep vein thrombosis in mice. Proc Natl Acad Sci U S A. 2013 May 21; 110(21):8674-9. View Abstract
Neutrophils release extracellular DNA traps during storage of red blood cell units. Transfusion. 2013 Dec; 53(12):3210-6. View Abstract
Lack of tryptophan hydroxylase-1 in mice results in gait abnormalities. PLoS One. 2013; 8(3):e59032. View Abstract
Neutrophil extracellular traps: A new link to cancer-associated thrombosis and potential implications for tumor progression. Oncoimmunology. 2013 Feb 01; 2(2):e22946. View Abstract
Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice. Blood. 2013 Feb 07; 121(6):1008-15. View Abstract
Isoflurane inhibits neutrophil recruitment in the cutaneous Arthus reaction model. J Anesth. 2013 Apr; 27(2):261-8. View Abstract
Endocytosis of soluble immune complexes leads to their clearance by Fc?RIIIB but induces neutrophil extracellular traps via Fc?RIIA in vivo. Blood. 2012 Nov 22; 120(22):4421-31. View Abstract
Protective anti-inflammatory effect of ADAMTS13 on myocardial ischemia/reperfusion injury in mice. Blood. 2012 Dec 20; 120(26):5217-23. View Abstract
Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis. Proc Natl Acad Sci U S A. 2012 Aug 07; 109(32):13076-81. View Abstract
ADAMTS13 exerts a thrombolytic effect in microcirculation. Thromb Haemost. 2012 Sep; 108(3):527-32. View Abstract
Shear-activated nanotherapeutics for drug targeting to obstructed blood vessels. Science. 2012 Aug 10; 337(6095):738-42. View Abstract
Extrahepatic high-density lipoprotein receptor SR-BI and apoA-I protect against deep vein thrombosis in mice. Arterioscler Thromb Vasc Biol. 2012 Aug; 32(8):1841-7. View Abstract
Neutrophil extracellular trap (NET) impact on deep vein thrombosis. Arterioscler Thromb Vasc Biol. 2012 Aug; 32(8):1777-83. View Abstract
Extracellular chromatin is an important mediator of ischemic stroke in mice. Arterioscler Thromb Vasc Biol. 2012 Aug; 32(8):1884-91. View Abstract
Circulating DNA and myeloperoxidase indicate disease activity in patients with thrombotic microangiopathies. Blood. 2012 Aug 09; 120(6):1157-64. View Abstract
Extracellular DNA traps are associated with the pathogenesis of TRALI in humans and mice. Blood. 2012 Jun 28; 119(26):6335-43. View Abstract
Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med. 2012 Apr 09; 209(4):819-35. View Abstract
ARC15105 is a potent antagonist of von Willebrand factor mediated platelet activation and adhesion. Arterioscler Thromb Vasc Biol. 2012 Apr; 32(4):902-9. View Abstract
Targeting platelet function to improve drug delivery. Oncoimmunology. 2012 Jan 01; 1(1):100-102. View Abstract
Neutrophil extracellular traps promote deep vein thrombosis in mice. J Thromb Haemost. 2012 Jan; 10(1):136-44. View Abstract
von Willebrand factor: an emerging target in stroke therapy. Stroke. 2012 Feb; 43(2):599-606. View Abstract
Desialylation accelerates platelet clearance after refrigeration and initiates GPIba metalloproteinase-mediated cleavage in mice. Blood. 2012 Feb 02; 119(5):1263-73. View Abstract
Platelet glycoprotein Iba is an important mediator of ischemic stroke in mice. Exp Transl Stroke Med. 2011 Sep 13; 3:9. View Abstract
Histones induce rapid and profound thrombocytopenia in mice. Blood. 2011 Sep 29; 118(13):3708-14. View Abstract
Rap1a activation by CalDAG-GEFI and p38 MAPK is involved in E-selectin-dependent slow leukocyte rolling. Eur J Immunol. 2011 Jul; 41(7):2074-85. View Abstract
The development of inflammatory joint disease is attenuated in mice expressing the anticoagulant prothrombin mutant W215A/E217A. Blood. 2011 Jun 09; 117(23):6326-37. View Abstract
Increased efficacy of breast cancer chemotherapy in thrombocytopenic mice. Cancer Res. 2011 Mar 01; 71(5):1540-9. View Abstract
von Willebrand factor-mediated platelet adhesion is critical for deep vein thrombosis in mouse models. Blood. 2011 Jan 27; 117(4):1400-7. View Abstract
The lack of ADAM17 activity during embryonic development causes hemorrhage and impairs vessel formation. PLoS One. 2010 Oct 15; 5(10):e13433. View Abstract
Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci U S A. 2010 Sep 07; 107(36):15880-5. View Abstract
A novel interaction between FlnA and Syk regulates platelet ITAM-mediated receptor signaling and function. J Exp Med. 2010 Aug 30; 207(9):1967-79. View Abstract
Integrin-independent role of CalDAG-GEFI in neutrophil chemotaxis. J Leukoc Biol. 2010 Aug; 88(2):313-9. View Abstract
p38 mitogen-activated protein kinase activation during platelet storage: consequences for platelet recovery and hemostatic function in vivo. Blood. 2010 Mar 04; 115(9):1835-42. View Abstract
Innate immune cells induce hemorrhage in tumors during thrombocytopenia. Am J Pathol. 2009 Oct; 175(4):1699-708. View Abstract
von Willebrand factor-cleaving protease ADAMTS13 reduces ischemic brain injury in experimental stroke. Blood. 2009 Oct 08; 114(15):3329-34. View Abstract
Platelets: guardians of tumor vasculature. Cancer Res. 2009 Jul 15; 69(14):5623-6. View Abstract
Differential stimulation of monocytic cells results in distinct populations of microparticles. J Thromb Haemost. 2009 Jun; 7(6):1019-28. View Abstract
Oxidative stress activates ADAM17/TACE and induces its target receptor shedding in platelets in a p38-dependent fashion. Cardiovasc Res. 2009 Oct 01; 84(1):137-44. View Abstract
Inhibition of VEGF or TGF-{beta} signaling activates endothelium and increases leukocyte rolling. Arterioscler Thromb Vasc Biol. 2009 Aug; 29(8):1185-92. View Abstract
Inhibition of von Willebrand factor-mediated platelet activation and thrombosis by the anti-von Willebrand factor A1-domain aptamer ARC1779. J Thromb Haemost. 2009 Jul; 7(7):1155-62. View Abstract
Elevated levels of soluble P-selectin in mice alter blood-brain barrier function, exacerbate stroke, and promote atherosclerosis. Blood. 2009 Jun 04; 113(23):6015-22. View Abstract
The distal carboxyl-terminal domains of ADAMTS13 are required for regulation of in vivo thrombus formation. Blood. 2009 May 21; 113(21):5323-9. View Abstract
The effect of C1 inhibitor on intestinal ischemia and reperfusion injury. Am J Physiol Gastrointest Liver Physiol. 2008 Nov; 295(5):G1042-9. View Abstract
Platelet granule secretion continuously prevents intratumor hemorrhage. Cancer Res. 2008 Aug 15; 68(16):6851-8. View Abstract
ADAMTS13: a new link between thrombosis and inflammation. J Exp Med. 2008 Sep 01; 205(9):2065-74. View Abstract
Peroxiredoxin1 prevents excessive endothelial activation and early atherosclerosis. Circ Res. 2008 Sep 12; 103(6):598-605. View Abstract
von-Willebrand factor influences blood brain barrier permeability and brain inflammation in experimental allergic encephalomyelitis. Am J Pathol. 2008 Sep; 173(3):892-900. View Abstract
CalDAG-GEFI and protein kinase C represent alternative pathways leading to activation of integrin alphaIIbbeta3 in platelets. Blood. 2008 Sep 01; 112(5):1696-703. View Abstract
The vessel wall and its interactions. Blood. 2008 Jun 01; 111(11):5271-81. View Abstract
Thrombocytopenia and platelet abnormalities in high-density lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol. 2008 Jun; 28(6):1111-6. View Abstract
Inflammation induces hemorrhage in thrombocytopenia. Blood. 2008 May 15; 111(10):4958-64. View Abstract
[Evaluation of T-cell interferon-gamma-release assays for the diagnosis of latent and active tuberculosis]. Dtsch Med Wochenschr. 2008 Feb; 133(8):354-7. View Abstract
Glycoprotein Ibalpha and von Willebrand factor in primary platelet adhesion and thrombus formation: lessons from mutant mice. Thromb Haemost. 2008 Feb; 99(2):264-70. View Abstract
The combined roles of ADAMTS13 and VWF in murine models of TTP, endotoxemia, and thrombosis. Blood. 2008 Apr 01; 111(7):3452-7. View Abstract
Prothrombotic effects of fibronectin isoforms containing the EDA domain. Arterioscler Thromb Vasc Biol. 2008 Feb; 28(2):296-301. View Abstract
Platelet adhesion receptors do not modulate infarct volume after a photochemically induced stroke in mice. Brain Res. 2007 Dec 14; 1185:239-45. View Abstract
PSGL-1 regulates platelet P-selectin-mediated endothelial activation and shedding of P-selectin from activated platelets. Thromb Haemost. 2007 Oct; 98(4):806-12. View Abstract
Dynamic visualization of thrombopoiesis within bone marrow. Science. 2007 Sep 21; 317(5845):1767-70. View Abstract
Mice lacking the signaling molecule CalDAG-GEFI represent a model for leukocyte adhesion deficiency type III. J Clin Invest. 2007 Jun; 117(6):1699-707. View Abstract
[Coil embolization of arteriovenous fistulae on in situ saphenous vein bypasses: success rate and complications]. Rofo. 2007 Jun; 179(6):587-92. View Abstract
In vitro function and phagocytosis of galactosylated platelet concentrates after long-term refrigeration. Transfusion. 2007 Mar; 47(3):442-51. View Abstract
Platelet adhesion receptors and their ligands in mouse models of thrombosis. Arterioscler Thromb Vasc Biol. 2007 Apr; 27(4):728-39. View Abstract
Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury. Proc Natl Acad Sci U S A. 2007 Jan 30; 104(5):1621-6. View Abstract
Formation of platelet strings and microthrombi in the presence of ADAMTS-13 inhibitor does not require P-selectin or beta3 integrin. J Thromb Haemost. 2007 Mar; 5(3):583-9. View Abstract
von Willebrand factor and factor VIII are independently required to form stable occlusive thrombi in injured veins. Blood. 2007 Mar 15; 109(6):2424-9. View Abstract
The role of platelet adhesion receptor GPIbalpha far exceeds that of its main ligand, von Willebrand factor, in arterial thrombosis. Proc Natl Acad Sci U S A. 2006 Nov 07; 103(45):16900-5. View Abstract
Mac-1 signaling via Src-family and Syk kinases results in elastase-dependent thrombohemorrhagic vasculopathy. Immunity. 2006 Aug; 25(2):271-83. View Abstract
ApoE deficiency leads to a progressive age-dependent blood-brain barrier leakage. Am J Physiol Cell Physiol. 2007 Apr; 292(4):C1256-62. View Abstract
Fibrinogen and von Willebrand factor-independent platelet aggregation in vitro and in vivo. J Thromb Haemost. 2006 Oct; 4(10):2230-7. View Abstract
The A2B adenosine receptor protects against inflammation and excessive vascular adhesion. J Clin Invest. 2006 Jul; 116(7):1913-23. View Abstract
Serum mannose-binding lectin deficiency is associated with cryptosporidiosis in young Haitian children. Clin Infect Dis. 2006 Aug 01; 43(3):289-94. View Abstract
Systemic antithrombotic effects of ADAMTS13. J Exp Med. 2006 Mar 20; 203(3):767-76. View Abstract
Decreased plasma fibronectin leads to delayed thrombus growth in injured arterioles. Arterioscler Thromb Vasc Biol. 2006 Jun; 26(6):1391-6. View Abstract
Platelets and platelet adhesion support angiogenesis while preventing excessive hemorrhage. Proc Natl Acad Sci U S A. 2006 Jan 24; 103(4):855-60. View Abstract
Activated platelets induce Weibel-Palade-body secretion and leukocyte rolling in vivo: role of P-selectin. Blood. 2005 Oct 01; 106(7):2334-9. View Abstract
A direct role for C1 inhibitor in regulation of leukocyte adhesion. J Immunol. 2005 May 15; 174(10):6462-6. View Abstract
New links between inflammation and thrombosis. Arterioscler Thromb Vasc Biol. 2005 Jul; 25(7):1321-4. View Abstract
Elevated soluble ICAM-1 levels induce immune deficiency and increase adiposity in mice. FASEB J. 2005 Jun; 19(8):1018-20. View Abstract
Torsemide versus furosemide after continuous renal replacement therapy due to acute renal failure in cardiac surgery patients. Ren Fail. 2005; 27(4):385-92. View Abstract
Tumor necrosis factor-alpha-converting enzyme (ADAM17) mediates GPIbalpha shedding from platelets in vitro and in vivo. Circ Res. 2004 Oct 01; 95(7):677-83. View Abstract
CalDAG-GEFI integrates signaling for platelet aggregation and thrombus formation. Nat Med. 2004 Sep; 10(9):982-6. View Abstract
ICAM-1 and beta2 integrin deficiency impairs fat oxidation and insulin metabolism during fasting. Mol Med. 2004 Jul-Dec; 10(7-12):72-9. View Abstract
GPVI down-regulation in murine platelets through metalloproteinase-dependent shedding. Thromb Haemost. 2004 May; 91(5):951-8. View Abstract
Mice lacking insulin or insulin-like growth factor 1 receptors in vascular endothelial cells maintain normal blood-brain barrier. Biochem Biophys Res Commun. 2004 Apr 30; 317(2):315-20. View Abstract
A new role in hemostasis for the adhesion receptor P-selectin. Trends Mol Med. 2004 Apr; 10(4):179-86. View Abstract
P-selectin and leukocyte microparticles are associated with venous thrombogenesis. J Vasc Surg. 2003 Nov; 38(5):1075-89. View Abstract
Nitric oxide regulates exocytosis by S-nitrosylation of N-ethylmaleimide-sensitive factor. Cell. 2003 Oct 17; 115(2):139-50. View Abstract
Platelets in inflammation and thrombosis. Arterioscler Thromb Vasc Biol. 2003 Dec; 23(12):2131-7. View Abstract
Metalloproteinase inhibitors improve the recovery and hemostatic function of in vitro-aged or -injured mouse platelets. Blood. 2003 Dec 01; 102(12):4229-35. View Abstract
Interaction of P-selectin and PSGL-1 generates microparticles that correct hemostasis in a mouse model of hemophilia A. Nat Med. 2003 Aug; 9(8):1020-5. View Abstract
Control of thrombus embolization and fibronectin internalization by integrin alpha IIb beta 3 engagement of the fibrinogen gamma chain. Blood. 2003 Nov 15; 102(10):3609-14. View Abstract
Plasma fibronectin promotes thrombus growth and stability in injured arterioles. Proc Natl Acad Sci U S A. 2003 Mar 04; 100(5):2415-9. View Abstract
Mechanisms and implications of platelet discoid shape. Blood. 2003 Jun 15; 101(12):4789-96. View Abstract
The clearance mechanism of chilled blood platelets. Cell. 2003 Jan 10; 112(1):87-97. View Abstract
Oxidized omega-3 fatty acids in fish oil inhibit leukocyte-endothelial interactions through activation of PPAR alpha. Blood. 2002 Aug 15; 100(4):1340-6. View Abstract
Role of syndecan-1 in leukocyte-endothelial interactions in the ocular vasculature. Invest Ophthalmol Vis Sci. 2002 Apr; 43(4):1135-41. View Abstract
CD40L stabilizes arterial thrombi by a beta3 integrin--dependent mechanism. Nat Med. 2002 Mar; 8(3):247-52. View Abstract
ApoE deficiency compromises the blood brain barrier especially after injury. Mol Med. 2001 Dec; 7(12):810-5. View Abstract
The isolation of antibiotic-resistant salmonella from retail ground meats. N Engl J Med. 2001 Oct 18; 345(16):1147-54. View Abstract
Localized reduction of atherosclerosis in von Willebrand factor-deficient mice. Blood. 2001 Sep 01; 98(5):1424-8. View Abstract
Increased thrombogenesis and embolus formation in mice lacking glycoprotein V. Blood. 2001 Jul 15; 98(2):368-73. View Abstract
Defect in regulated secretion of P-selectin affects leukocyte recruitment in von Willebrand factor-deficient mice. Proc Natl Acad Sci U S A. 2001 Mar 27; 98(7):4072-7. View Abstract
Interleukin 11 significantly increases plasma von Willebrand factor and factor VIII in wild type and von Willebrand disease mouse models. Blood. 2001 Jan 15; 97(2):465-72. View Abstract
Pro-coagulant state resulting from high levels of soluble P-selectin in blood. Proc Natl Acad Sci U S A. 2000 Dec 05; 97(25):13835-40. View Abstract
Platelets adhere to and translocate on von Willebrand factor presented by endothelium in stimulated veins. Blood. 2000 Nov 15; 96(10):3322-8. View Abstract
Sleep and wakefulness in c-fos and fos B gene knockout mice. Brain Res Mol Brain Res. 2000 Aug 14; 80(1):75-87. View Abstract
Persistence of platelet thrombus formation in arterioles of mice lacking both von Willebrand factor and fibrinogen. J Clin Invest. 2000 Aug; 106(3):385-92. View Abstract
Prominent role of P-selectin in the development of advanced atherosclerosis in ApoE-deficient mice. Circulation. 2000 May 16; 101(19):2290-5. View Abstract
P-Selectin glycoprotein ligand 1 (PSGL-1) is expressed on platelets and can mediate platelet-endothelial interactions in vivo. J Exp Med. 2000 Apr 17; 191(8):1413-22. View Abstract
Distribution of hypocretin-containing neurons in the lateral hypothalamus and C-fos-immunoreactive neurons in the VLPO. Sleep Res Online. 2000; 3(1):35-42. View Abstract
Insights from von Willebrand disease animal models. Cell Mol Life Sci. 1999 Dec; 56(11-12):977-90. View Abstract
Carboxypeptidase E does not mediate von Willebrand factor targeting to storage granules. Eur J Cell Biol. 1999 Dec; 78(12):884-91. View Abstract
Multiple, targeted deficiencies in selectins reveal a predominant role for P-selectin in leukocyte recruitment. Proc Natl Acad Sci U S A. 1999 Sep 28; 96(20):11452-7. View Abstract
Targeted disruption of cd39/ATP diphosphohydrolase results in disordered hemostasis and thromboregulation. Nat Med. 1999 Sep; 5(9):1010-7. View Abstract
New discoveries with mice mutant in endothelial and platelet selectins. Thromb Haemost. 1999 Aug; 82(2):850-7. View Abstract
P- and E-selectin-deficient mice are susceptible to cerebral ischemia-reperfusion injury. Brain Res. 1999 Jul 24; 835(2):360-4. View Abstract
Donor MHC and adhesion molecules in transplant arteriosclerosis. J Clin Invest. 1999 Feb; 103(4):469-74. View Abstract
Selective eosinophil transendothelial migration triggered by eotaxin via modulation of Mac-1/ICAM-1 and VLA-4/VCAM-1 interactions. Int Immunol. 1999 Jan; 11(1):1-10. View Abstract
P-Selectin and platelet clearance. Blood. 1998 Dec 01; 92(11):4446-52. View Abstract
Endothelial selectins and vascular cell adhesion molecule-1 promote hematopoietic progenitor homing to bone marrow. Proc Natl Acad Sci U S A. 1998 Nov 24; 95(24):14423-8. View Abstract
Role of P-selectin cytoplasmic domain in granular targeting in vivo and in early inflammatory responses. J Cell Biol. 1998 Nov 16; 143(4):1129-41. View Abstract
Overlapping functions of E- and P-selectin in neutrophil recruitment during acute inflammation. Blood. 1998 Oct 01; 92(7):2345-52. View Abstract
E and P selectins are not required for resistance to severe murine lyme arthritis. Infect Immun. 1998 Sep; 66(9):4557-9. View Abstract
A mouse model of severe von Willebrand disease: defects in hemostasis and thrombosis. Proc Natl Acad Sci U S A. 1998 Aug 04; 95(16):9524-9. View Abstract
Hematopoietic progenitor cell rolling in bone marrow microvessels: parallel contributions by endothelial selectins and vascular cell adhesion molecule 1. J Exp Med. 1998 Aug 03; 188(3):465-74. View Abstract
The combined role of P- and E-selectins in atherosclerosis. J Clin Invest. 1998 Jul 01; 102(1):145-52. View Abstract
Determination of endogenous growth factors in human wound fluid: temporal presence and profiles of secretion. Plast Reconstr Surg. 1998 Jul; 102(1):117-23. View Abstract
The transmembrane domain enhances granular targeting of P-selectin. Eur J Cell Biol. 1998 Apr; 75(4):331-43. View Abstract
P- and E-selectins are required for the leukocyte recruitment, but not the tissue swelling, associated with IgE- and mast cell-dependent inflammation in mouse skin. Lab Invest. 1998 Apr; 78(4):497-505. View Abstract
Angiogenesis in P- and E-selectin-deficient mice. Microcirculation. 1998; 5(2-3):173-8. View Abstract
Genetic manipulation of vascular adhesion molecules in mice. J Clin Invest. 1997 Dec 01; 100(11 Suppl):S11-3. View Abstract
Experimental murine acid aspiration injury is mediated by neutrophils and the alternative complement pathway. J Appl Physiol (1985). 1997 Oct; 83(4):1090-5. View Abstract
Generation and characterization of a novel adhesion function blocking monoclonal antibody recognizing both rat and mouse E-selectin. Hybridoma. 1997 Aug; 16(4):355-61. View Abstract
A new class of obesity genes encodes leukocyte adhesion receptors. Proc Natl Acad Sci U S A. 1997 Jul 08; 94(14):7526-30. View Abstract
Insights into selectin function from knockout mice. Thromb Haemost. 1997 Jul; 78(1):60-4. View Abstract
Characterization of a novel adhesion function blocking monoclonal antibody to rat/mouse P-selectin generated in the P-selectin-deficient mouse. Hybridoma. 1997 Jun; 16(3):249-57. View Abstract
Role of endothelial selectins in wound repair. Am J Pathol. 1997 May; 150(5):1701-9. View Abstract
L-[1-(13)C] Phenylalanine oxidation as a measure of hepatocyte functional capacity in end-stage liver disease. Am J Surg. 1997 Apr; 173(4):270-3; discussion 273-4. View Abstract
Absence of P-selectin delays fatty streak formation in mice. J Clin Invest. 1997 Mar 01; 99(5):1037-43. View Abstract
Role of the Brn-3 family of POU-domain genes in the development of the auditory/vestibular, somatosensory, and visual systems. Cold Spring Harb Symp Quant Biol. 1997; 62:325-36. View Abstract
Genetic manipulation of vascular adhesion molecules in mice. J Clin Invest. 1996 Nov 15; 98(10):2193-5. View Abstract
Control of rod retinomotor movements in teleost retinae: the role of dopamine in mediating light-dependent and circadian signals. Cell Tissue Res. 1996 Sep; 285(3):445-51. View Abstract
Adhesion molecules--Part II: Blood vessels and blood cells. N Engl J Med. 1996 Jul 04; 335(1):43-5. View Abstract
Adhesion molecules--Part 1. N Engl J Med. 1996 Jun 06; 334(23):1526-9. View Abstract
Cytokine-induced meningitis is dramatically attenuated in mice deficient in endothelial selectins. J Clin Invest. 1996 Jun 01; 97(11):2485-90. View Abstract
Double knockout highlights value of endothelial selectins. Immunol Today. 1996 May; 17(5):205. View Abstract
Susceptibility to infection and altered hematopoiesis in mice deficient in both P- and E-selectins. Cell. 1996 Feb 23; 84(4):563-74. View Abstract
Defects in hemostasis in P-selectin-deficient mice. Blood. 1996 Feb 15; 87(4):1238-42. View Abstract
Hypoxia-induced exocytosis of endothelial cell Weibel-Palade bodies. A mechanism for rapid neutrophil recruitment after cardiac preservation. J Clin Invest. 1996 Jan 15; 97(2):493-500. View Abstract
Rolling in P-selectin-deficient mice is reduced but not eliminated in the dorsal skin. Blood. 1995 Nov 01; 86(9):3487-92. View Abstract
Blood cell dynamics in P-selectin-deficient mice. Blood. 1995 Aug 01; 86(3):1106-14. View Abstract
Platelets roll on stimulated endothelium in vivo: an interaction mediated by endothelial P-selectin. Proc Natl Acad Sci U S A. 1995 Aug 01; 92(16):7450-4. View Abstract
Reduced recruitment of inflammatory cells in a contact hypersensitivity response in P-selectin-deficient mice. J Exp Med. 1995 Jun 01; 181(6):2277-82. View Abstract
P-selectin knockout: a mouse model for various human diseases. Ciba Found Symp. 1995; 189:2-10; discussion 10-16, 77-8. View Abstract
von Willebrand factor proteolytic processing and multimerization precede the formation of Weibel-Palade bodies. Blood. 1994 Jun 15; 83(12):3536-44. View Abstract
Requirement for both D domains of the propolypeptide in von Willebrand factor multimerization and storage. Thromb Haemost. 1993 Dec 20; 70(6):1053-7. View Abstract
CD63 is a component of Weibel-Palade bodies of human endothelial cells. Blood. 1993 Aug 15; 82(4):1184-91. View Abstract
Leukocyte rolling and extravasation are severely compromised in P selectin-deficient mice. Cell. 1993 Aug 13; 74(3):541-54. View Abstract
P-selectin mediates adhesion of platelets to neuroblastoma and small cell lung cancer. J Clin Invest. 1993 Aug; 92(2):804-13. View Abstract
Divergent fates of P- and E-selectins after their expression on the plasma membrane. Mol Biol Cell. 1993 Aug; 4(8):791-801. View Abstract
The Weibel-Palade body: the storage granule for von Willebrand factor and P-selectin. Thromb Haemost. 1993 Jul 01; 70(1):105-10. View Abstract
COP1, an Arabidopsis regulatory gene, encodes a protein with both a zinc-binding motif and a G beta homologous domain. Cell. 1992 Nov 27; 71(5):791-801. View Abstract
P-selectin and E-selectin. Distinct but overlapping leukocyte ligand specificities. J Biol Chem. 1992 Jun 05; 267(16):11104-10. View Abstract
Vicinal cysteines in the prosequence play a role in von Willebrand factor multimer assembly. Proc Natl Acad Sci U S A. 1992 Apr 15; 89(8):3531-5. View Abstract
A 130-kDa protein on endothelial cells binds to amino acids 15-42 of the B beta chain of fibrinogen. J Biol Chem. 1992 Feb 05; 267(4):2451-8. View Abstract
P-selectin, a granule membrane protein of platelets and endothelial cells, follows the regulated secretory pathway in AtT-20 cells. J Cell Biol. 1992 Feb; 116(3):617-25. View Abstract
von Willebrand factor and the endothelium. Mayo Clin Proc. 1991 Jun; 66(6):621-7. View Abstract
Induction of specific storage organelles by von Willebrand factor propolypeptide. Cell. 1991 Jan 25; 64(2):403-13. View Abstract
von Willebrand factor biosynthesis and processing. Ann N Y Acad Sci. 1991; 614:153-66. View Abstract
PADGEM, a leukocyte receptor on activated platelets. Biology and application to in vivo medical diagnostics. Curr Stud Hematol Blood Transfus. 1991; (58):32-6. View Abstract
PADGEM-dependent adhesion of platelets to monocytes and neutrophils is mediated by a lineage-specific carbohydrate, LNF III (CD15). Cell. 1990 Nov 02; 63(3):467-74. View Abstract
Human endothelial cells synthesize, process, and secrete fibronectin molecules bearing an alternatively spliced type III homology (ED1). Blood. 1990 May 01; 75(9):1801-8. View Abstract
Cell biology of von Willebrand factor. Annu Rev Cell Biol. 1990; 6:217-46. View Abstract
PADGEM protein: a receptor that mediates the interaction of activated platelets with neutrophils and monocytes. Cell. 1989 Oct 20; 59(2):305-12. View Abstract
In vitro multimerization of von Willebrand factor is triggered by low pH. Importance of the propolypeptide and free sulfhydryls. J Biol Chem. 1989 Aug 15; 264(23):13497-503. View Abstract
Mediation of fibrin-induced release of von Willebrand factor from cultured endothelial cells by the fibrin beta chain. J Clin Invest. 1989 Aug; 84(2):435-42. View Abstract
Differing polarity of the constitutive and regulated secretory pathways for von Willebrand factor in endothelial cells. J Cell Biol. 1989 Apr; 108(4):1283-9. View Abstract
Temperature-sensitive steps in the secretory pathway for von Willebrand factor in endothelial cells. Eur J Cell Biol. 1989 Apr; 48(2):337-43. View Abstract
PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells. Blood. 1989 Apr; 73(5):1109-12. View Abstract
von Willebrand factor biosynthesis and partitioning between constitutive and regulated pathways of secretion after thrombin stimulation. Blood. 1989 Feb 15; 73(3):706-11. View Abstract
Molecular and cellular biology of von Willebrand factor. Prog Hemost Thromb. 1989; 9:233-59. View Abstract
Intact microtubules are necessary for complete processing, storage and regulated secretion of von Willebrand factor by endothelial cells. Eur J Cell Biol. 1987 Jun; 43(3):377-83. View Abstract
von Willebrand factor released from Weibel-Palade bodies binds more avidly to extracellular matrix than that secreted constitutively. Blood. 1987 May; 69(5):1531-4. View Abstract
Divergent fates of von Willebrand factor and its propolypeptide (von Willebrand antigen II) after secretion from endothelial cells. Proc Natl Acad Sci U S A. 1987 Apr; 84(7):1955-9. View Abstract
Topology and order of formation of interchain disulfide bonds in von Willebrand factor. Blood. 1987 Jan; 69(1):27-32. View Abstract
Fibrin induces release of von Willebrand factor from endothelial cells. J Clin Invest. 1987 Jan; 79(1):117-23. View Abstract
Inducible secretion of large, biologically potent von Willebrand factor multimers. Cell. 1986 Jul 18; 46(2):185-90. View Abstract
Propolypeptide of von Willebrand factor circulates in blood and is identical to von Willebrand antigen II. Science. 1986 May 23; 232(4753):995-8. View Abstract
Initial glycosylation and acidic pH in the Golgi apparatus are required for multimerization of von Willebrand factor. J Cell Biol. 1986 Apr; 102(4):1320-4. View Abstract
Biosynthesis of von Willebrand protein by human megakaryocytes. J Clin Invest. 1985 Sep; 76(3):1102-6. View Abstract
Inhibition of disulfide bonding of von Willebrand protein by monensin results in small, functionally defective multimers. J Cell Biol. 1985 Jul; 101(1):112-20. View Abstract
Biosynthesis of von Willebrand protein by human endothelial cells: processing steps and their intracellular localization. J Cell Biol. 1984 Dec; 99(6):2123-30. View Abstract
Irradiation induces release of von Willebrand protein from endothelial cells in culture. Blood. 1984 Aug; 64(2):567-70. View Abstract
Von Willebrand protein binds to extracellular matrices independently of collagen. Proc Natl Acad Sci U S A. 1984 Jan; 81(2):471-5. View Abstract
Biosynthesis of von Willebrand protein by human endothelial cells. Identification of a large precursor polypeptide chain. J Biol Chem. 1983 Feb 25; 258(4):2065-7. View Abstract
Immunolocalization of von Willebrand protein in Weibel-Palade bodies of human endothelial cells. J Cell Biol. 1982 Oct; 95(1):355-60. View Abstract
Fibronectin-coated beads are endocytosed by cells and align with microfilament bundles. Exp Cell Res. 1982 Aug; 140(2):373-81. View Abstract
Relationships between microfilaments, cell-substratum adhesion, and fibronectin. Cold Spring Harb Symp Quant Biol. 1982; 46 Pt 2:659-70. View Abstract
Similarities and differences between the fibronectins of normal and transformed hamster cells. J Biol Chem. 1981 Nov 25; 256(22):11708-15. View Abstract
Topological arrangement of the major structural features of fibronectin. J Biol Chem. 1980 May 10; 255(9):4304-12. View Abstract
Domain structure of fibronectin and its relation to function. Disulfides and sulfhydryl groups. J Biol Chem. 1979 Jul 25; 254(14):6746-54. View Abstract