0000000000194965
AUTHOR
Jennifer Royce
EPCR Signaling Controls the Activity of Hematopoietic Stem Cells Independent of Coagulation Regulation
Abstract Background All mature blood cells are derived from multipotent hematopoietic stem cells (HSCs) which are activated to meet the demand of the host during inflammation and injury. The endothelial cell protein C receptor (EPCR) is a marker for primitivity and quiescence of HSCs but the relative contributions of EPCR signaling versus anticoagulant functions in HSC maintenance are incompletely defined. Aims We aimed to dissect functions of EPCR by studying anticoagulant and signaling function in HSC of EPCR C/S mice carrying a single intracellular point mutation abolishing normal trafficking of EPCR through endo-lysosomal compartments. We assessed the contributions of EPCR signaling to …
Gpibα Engagement Induces Activation of Human Platelet TF and Association with Constitutively Platelet Surface-Bound FVIIa
The membranes of activated platelets assemble clotting protein complexes and enzymatic reactions needed for hemostasis and causing pathological thrombosis. Several reports have shown that human platelets contain TF, but controversies remain on the functional contributions of platelet TF to coagulation initiation. Here, we delineate the mechanism that converts platelet-associated TF to a procoagulant molecule. By combining specific inhibitors with human platelets from normal probands or patients with Glanzmann thrombasthenia or homozygous GPVI deficiency, we analyzed the procoagulant activation of platelet TF by biochemical methods, confocal microscopy, platelet adhesion under flow on VWF an…
Lipid presentation by the protein C receptor links coagulation with autoimmunity.
A lipid-protein autoimmunity target Several autoimmune diseases, including systemic lupus erythematosus and primary antiphospholipid syndrome, are characterized by the presence of antiphospholipid antibodies (aPLs). These molecules can activate the complement and coagulation cascades, which contributes to pathologies such as thrombosis, stroke, and pregnancy complications. Müller-Calleja et al. found that endothelial protein C receptor (EPCR) in complex with lysobisphosphatidic acid (LBPA) is the cell-surface target for aPL and mediates its internalization (see the Perspective by Kaplan). aPL binding to EPCR-LBPA resulted in the activation of tissue factor–mediated coagulation and interfero…