Alexander Brill
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View article: Spleen Tyrosine Kinase Inhibition Mitigates Hemin-Induced Thromboinflammation in an Organ-Specific Manner in Sickle Cell Mice
Spleen Tyrosine Kinase Inhibition Mitigates Hemin-Induced Thromboinflammation in an Organ-Specific Manner in Sickle Cell Mice Open
BACKGROUND: Sickle cell disease (SCD) is a challenging genetic disorder characterized by hemolytic anemia, vaso-occlusive crises (VOC), and progressive organ damage. Despite its severity, effective treatments are limited. The recent withdr…
View article: Editorial: Inflammation and immune factors in venous thromboembolism
Editorial: Inflammation and immune factors in venous thromboembolism Open
This collection of articles provides a comprehensive and timely overview of the multifaceted roles that immune and inflammatory mechanisms play in thrombus development and progression, highlights several critical aspects of the role of inf…
View article: Venous thrombosis unchained: Pandora’s box of noninflammatory mechanisms
Venous thrombosis unchained: Pandora’s box of noninflammatory mechanisms Open
Venous thromboembolism, which includes deep vein thrombosis (DVT) and pulmonary embolism, represents a complex pathological process extending far beyond inflammatory mechanisms. This review comprehensively examines the multifaceted noninfl…
View article: Selective Btk inhibition by PRN1008/PRN473 blocks human CLEC-2, and PRN473 reduces venous thrombosis formation in mice
Selective Btk inhibition by PRN1008/PRN473 blocks human CLEC-2, and PRN473 reduces venous thrombosis formation in mice Open
Platelet C-type lectin-like receptor 2 (CLEC-2) is a hem-immunoreceptor tyrosine–based activation motif-containing receptor that has a critical role in venous thrombosis but minimal involvement in hemostasis. CLEC-2 can be blocked by Btk i…
View article: Hot under the clot: venous thrombogenesis is an inflammatory process
Hot under the clot: venous thrombogenesis is an inflammatory process Open
Venous thrombosis (VT) is a serious medical condition in which a blood clot forms in deep veins, often causing limb swelling and pain. Current antithrombotic therapies carry significant bleeding risks resulting from targeting essential coa…
View article: Spleen tyrosine kinase inhibition mitigates hemin-induced thromboinflammation in the lung and kidney of sickle cell mice
Spleen tyrosine kinase inhibition mitigates hemin-induced thromboinflammation in the lung and kidney of sickle cell mice Open
Sickle cell disease (SCD) leads to hemolytic anemia, vaso-occlusive crisis (VOC), hypoperfusion, and progressive organ damage. Hemin, released during hemolysis in SCD, induces platelet activation through CLEC-2, endothelial activation thro…
View article: Hydroxychloroquine inhibits hemolysis-induced arterial thrombosis ex vivo and improves lung perfusion in hemin-treated mice
Hydroxychloroquine inhibits hemolysis-induced arterial thrombosis ex vivo and improves lung perfusion in hemin-treated mice Open
Hydroxychloroquine inhibited hemolysis-induced arterial thrombosis ex vivo and improved pulmonary perfusion in hemin-treated mice, supporting a potential benefit of its use as an adjuvant therapy in hemolytic diseases to limit arterial thr…
View article: Megakaryocyte NLRP3 hyperactivation induces mild anemia and potentiates inflammatory response in mice
Megakaryocyte NLRP3 hyperactivation induces mild anemia and potentiates inflammatory response in mice Open
Background The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome has been described in both immune cells and platelets, but its role in the megakaryocyte (MK) lineage remains elusive. Objective The aim of this study wa…
View article: Platelet accumulation in an endothelium-coated elastic vein valve model of deep vein thrombosis is mediated by GPIbα—VWF interaction
Platelet accumulation in an endothelium-coated elastic vein valve model of deep vein thrombosis is mediated by GPIbα—VWF interaction Open
Deep vein thrombosis is a life-threatening disease that takes millions of people's lives worldwide. Given both technical and ethical issues of using animals in research, it is necessary to develop an appropriate in vitro model that would r…
View article: Megakaryocyte NLRP3 hyperactivation induces anemia and potentiates inflammatory response in mice
Megakaryocyte NLRP3 hyperactivation induces anemia and potentiates inflammatory response in mice Open
The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome has been described in both immune cells and platelets but its role in the megakaryocyte (MK) lineage remains elusive. Here, we generated Nlrp3A350V/+/Gp1ba-CreKI/+ m…
View article: Severity of SARS-CoV-2 infection is associated with high numbers of alveolar mast cells and their degranulation
Severity of SARS-CoV-2 infection is associated with high numbers of alveolar mast cells and their degranulation Open
Background The systemic inflammatory response post-SARS-CoV-2 infection increases pro-inflammatory cytokine production, multi-organ damage, and mortality rates. Mast cells (MC) modulate thrombo-inflammatory disease progression ( e.g. , dee…
View article: Critical role for platelet Ral GTPases in regulating neutrophil extracellular traps and venous thrombosis in mice
Critical role for platelet Ral GTPases in regulating neutrophil extracellular traps and venous thrombosis in mice Open
Deep vein thrombosis (DVT) is a multifactorial disease whose incidence is a major global burden on morbidity and mortality rates. While the pathophysiology of the disease is still being uncovered, increasing evidence suggests a more promin…
View article: Neutrophils Mediate Pulmonary Artery Thrombosis In Situ
Neutrophils Mediate Pulmonary Artery Thrombosis In Situ Open
Pulmonary embolism is a life-threatening condition, which can result in respiratory insufficiency and death. Blood clots occluding branches of the pulmonary artery (PA) are traditionally considered to originate from thrombi in deep veins (…
View article: Modelling Particle Agglomeration on through Elastic Valves under Flow
Modelling Particle Agglomeration on through Elastic Valves under Flow Open
This work proposes a model of particle agglomeration in elastic valves replicating the geometry and the fluid dynamics of a venous valve. The fluid dynamics is simulated with Smooth Particle Hydrodynamics, the elastic leaflets of the valve…
View article: CLEC-2 Prevents Accumulation and Retention of Inflammatory Macrophages During Murine Peritonitis
CLEC-2 Prevents Accumulation and Retention of Inflammatory Macrophages During Murine Peritonitis Open
Platelets play a key role in the development, progression and resolution of the inflammatory response during sterile inflammation and infection, although the mechanism is not well understood. Here we show that platelet CLEC-2 reduces tissu…
View article: Neutrophil extracellular traps and inflammasomes cooperatively promote venous thrombosis in mice
Neutrophil extracellular traps and inflammasomes cooperatively promote venous thrombosis in mice Open
Deep vein thrombosis (DVT) is linked to local inflammation. A role for both neutrophil extracellular traps (NETs) and the assembly of inflammasomes (leading to caspase-1–dependent interleukin-1β activation) in the development of DVT was re…
View article: Multiple Facets of Venous Thrombosis
Multiple Facets of Venous Thrombosis Open
Venous thromboembolism, a complex disease combining deep vein thrombosis (DVT) and its most dangerous complication, pulmonary embolism (PE), strikes millions of people worldwide [...]
View article: CLEC-2 promotes inflammatory peritoneal macrophage emigration to draining lymph nodes during endotoxemia
CLEC-2 promotes inflammatory peritoneal macrophage emigration to draining lymph nodes during endotoxemia Open
Macrophage recruitment during sterile inflammation and infection is essential to clear pathogens, apoptotic cells and debris. However, persistent macrophage accumulation leads to chronic inflammation. Platelets are emerging as key modulato…
View article: Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo
Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo Open
Deep vein thrombosis (DVT) is a major cause of cardiovascular death. The sequence of events that promote DVT remains obscure, largely as a result of the lack of an appropriate rodent model. We describe a novel mouse model of DVT which repr…
View article: The role of valve stiffness in the insurgence of deep vein thrombosis
The role of valve stiffness in the insurgence of deep vein thrombosis Open
Deep vein thrombosis is a life-threatening development of blood clots in deep veins. Immobility and blood flow stagnancy are typical risk factors indicating that fluid dynamics play an important role in the initiation of venous clots. Howe…
View article: Pulmonary Artery Thrombosis: A Diagnosis That Strives for Its Independence
Pulmonary Artery Thrombosis: A Diagnosis That Strives for Its Independence Open
According to a widespread theory, thrombotic masses are not formed in the pulmonary artery (PA) but result from migration of blood clots from the venous system. This concept has prevailed in clinical practice for more than a century. Howev…
View article: Low-dose Btk inhibitors selectively block platelet activation by CLEC-2
Low-dose Btk inhibitors selectively block platelet activation by CLEC-2 Open
Inhibitors of the tyrosine kinase Btk have been proposed as novel antiplatelet agents. In this study we show that low concentrations of the Btk inhibitor ibrutinib block CLEC-2-mediated activation and tyrosine phosphorylation including Syk…
View article: Appropriation of GPIbα from platelet-derived extracellular vesicles supports monocyte recruitment in systemic inflammation
Appropriation of GPIbα from platelet-derived extracellular vesicles supports monocyte recruitment in systemic inflammation Open
Interactions between platelets, leukocytes and the vessel wall provide alternative pathological routes of thrombo-inflammatory leukocyte recruitment. We found that when platelets were activated by a range of agonists in whole blood, they s…