A5031898067- Platelet Disorders and Treatments
- Cell Adhesion Molecules Research
- Heparin-Induced Thrombocytopenia and Thrombosis
- Blood Coagulation and Thrombosis Mechanisms
- Blood disorders and treatments
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Blood properties and coagulation
- Protease and Inhibitor Mechanisms
- Venous Thromboembolism Diagnosis and Management
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Antiplatelet Therapy and Cardiovascular Diseases
- Chemical Reactions and Isotopes
- Chemokine receptors and signaling
- Immune Response and Inflammation
- Sepsis Diagnosis and Treatment
- Hemophilia Treatment and Research
- Chronic Myeloid Leukemia Treatments
- Extracellular vesicles in disease
- Monoclonal and Polyclonal Antibodies Research
- Atherosclerosis and Cardiovascular Diseases
- Neonatal and Maternal Infections
- Radiation Effects and Dosimetry
- MicroRNA in disease regulation
- Proteoglycans and glycosaminoglycans research
- Immune cells in cancer
Children's Hospital of Philadelphia
2014-2024
Institute for Medical Biology
2015-2024
Polish Academy of Sciences
2016-2024
University of Pennsylvania
2004-2023
Pediatrics and Genetics
2020
Central Laboratory for Radiological Protection
1985-2016
Weston Solutions (United States)
2013
University of California, San Diego
2009
University of Minnesota
2009
Howard Hughes Medical Institute
2009
Abstract Coagulation has long been known to facilitate metastasis. To pinpoint the steps where coagulation might play a role in metastasis, we used three-dimensional visualization of direct infusion fluorescence labeled antibody observe interaction tumor cells with platelets and fibrinogen isolated lung preparations. Tumor arrested pulmonary vasculature were associated clot composed both fibrin(ogen). Initially, attached vessels rounded. Over next 2 6 hours, they spread on vessel surface....
Heterotrimeric G proteins mediate the earliest step in cell responses to external events by linking surface receptors intracellular signaling pathways. z is a member of i family that prominently expressed platelets and brain. Here, we show deletion α subunit mice: ( ) impairs platelet aggregation preventing inhibition cAMP formation normally seen at physiologic concentrations epinephrine, ii causes mice be more resistant fatal thromboembolism. Loss zα also results greatly exaggerated...
Liver fibrosis is a major cause of morbidity and mortality worldwide. Platelets are involved in liver damage, but the underlying molecular mechanisms remain elusive. Here, we investigate platelet-derived chemokine (C-X-C motif) ligand 4 (CXCL4) as mediator fibrotic damage. Serum concentrations intrahepatic messenger RNA CXCL4 were measured patients with chronic diseases mice after toxic injury. Platelet aggregation early was determined by electron microscopy immunohistochemistry mice....
Activated platelets, which release platelet factor 4 (PF4) are present in patients with atherosclerosis. To date, no direct in-vivo evidence exists for the involvement of PF4 atherogenesis. In current study, we tested hypothesis that is atherogenic, and genetic elimination would protect mice from We have bred PF4(-/-) onto two athero-susceptible backgrounds, WT-C57Bl/6(WT) apoE(-/-) to examine importance order induce atherosclerosis, WT were fed an atherogenic diet 30 weeks, while a high-fat...
Heparin-induced thrombocytopenia (HIT) is an immune-mediated thrombocytopenic disorder associated with a severe prothrombotic state. We investigated whether neutrophils and neutrophil extracellular traps (NETs) contribute to the development of thrombosis in HIT. Using endothelialized microfluidic system murine passive immunization model, we show that HIT induction leads increased adherence venous endothelium. In mice, endothelial enhanced immediately downstream nascent thrombi, after which...
Fibrosis is a major cause of mortality worldwide, characterized by myofibroblast activation and excessive extracellular matrix deposition. Systemic sclerosis prototypic fibrotic disease in which CXCL4 increased strongly correlates with skin lung fibrosis. Here we aim to elucidate the role fibrosis development. levels are multiple inflammatory mouse models, and, using CXCL4-deficient mice, demonstrate essential promoting events skin, lungs, heart. Overexpressing human mice aggravates, whereas...
Accumulation of low-density lipoprotein (LDL)-derived cholesterol by macrophages in vessel walls is a pathogenomic feature atherosclerotic lesions. Platelets contribute to lipid uptake through mechanisms that are only partially understood. We have previously shown platelet factor 4 (PF4) inhibits the binding and degradation LDL its receptor, process could promote formation oxidized (ox-LDL). now characterized effect PF4 on ox-LDL vascular cells accumulation esters. bound directly also...
Thrombopoiesis, the process by which circulating platelets arise from megakaryocytes, remains incompletely understood. Prior studies suggest that megakaryocytes shed in pulmonary vasculature. To better understand thrombopoiesis and to develop a potential platelet transfusion strategy is not dependent upon donors, of there shortage, we examined whether infused into mice platelets. Infused led clinically relevant increases numbers. The released were normal size, displayed appropriate surface...
Th cells are the major effector in transplant rejection and can be divided into Th1, Th2, Th17, Treg subsets. differentiation is controlled by transcription factor expression, which driven positive negative cytokine chemokine stimuli at time of T cell activation. Here we discovered that platelet 4 (PF4) a regulator Th17 differentiation. PF4-deficient platelet-deficient mice had exaggerated immune responses to cardiac transplantation, including increased numbers infiltrating plasma IL-17....
Platelets and neutrophils contribute to the development of acute lung injury (ALI). However, mechanism by which platelets make this contribution is incompletely understood. We investigated whether two most abundant platelet chemokines, CXCL7, induces neutrophil chemotaxis activation, CXCL4, does neither, mediate ALI through complementary pathogenic pathways. To examine role platelet-derived chemokines in pathogenesis using Cxcl7-/- Cxcl4-/- knockout mice that express human CXCL7 or we...