0000000000590388
AUTHOR
T. Son Nguyen
Macrophage protease-activated receptor 2 regulates fetal liver erythropoiesis in mice.
AbstractDeficiencies in many coagulation factors and protease-activated receptors (PARs) affect embryonic development. We describe a defect in definitive erythropoiesis in PAR2-deficient mice. Embryonic PAR2 deficiency increases embryonic death associated with variably severe anemia in comparison with PAR2-expressing embryos. PAR2-deficient fetal livers display reduced macrophage densities, erythroblastic island areas, and messenger RNA expression levels of markers for erythropoiesis and macrophages. Coagulation factor synthesis in the liver coincides with expanding fetal liver hematopoiesis during midgestation, and embryonic factor VII (FVII) deficiency impairs liver macrophage development…
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…
Extravascular coagulation in hematopoietic stem and progenitor cell regulation
Abstract The hemostatic system plays pivotal roles in injury repair, innate immunity, and adaptation to inflammatory challenges. We review the evidence that these vascular-protective mechanisms have nontraditional roles in hematopoietic stem cell (HSC) maintenance in their physiological bone marrow (BM) niches at steady-state and under stress. Expression of coagulation factors and the extrinsic coagulation initiator tissue factor by osteoblasts, tissue-resident macrophages, and megakaryocytes suggests that endosteal and vascular HSC niches are functionally regulated by extravascular coagulation. The anticoagulant endothelial protein C receptor (EPCR; Procr) is highly expressed by primitive …