ArticleThe Journal of clinical investigation2010
Activated protein C targets CD8+ dendritic cells to reduce the mortality of endotoxemia in mice.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 93 citations in OpenAlex.
- Review
- Lipid nanoparticles as a tool to dissect dendritic cell maturation pathways.Cell reports · 2025Article
- An orthosteric/allosteric bivalent peptide agonist comprising covalently linked protease-activated receptor-derived peptides mimics in vitro and in vivo activities of activated protein C.Journal of thrombosis and haemostasis : JTH · 2024Article
- Endothelial Protein C Receptor and Its Impact on Rheumatic Disease.Journal of clinical medicine · 2024Review
- EPCR deficiency ameliorates inflammatory arthritis in mice by suppressing the activation and migration of T cells and dendritic cells.Rheumatology (Oxford, England) · 2024Article
- Activated protein C modulates T-cell metabolism and epigenetic FOXP3 induction via α-ketoglutarate.Blood advances · 2023Article
- EPCR-PAR1 biased signaling regulates perfusion recovery and neovascularization in peripheral ischemia.JCI insight · 2022Article
- Apolipoprotein A-I enhances activated protein C cytoprotective activity.Blood advances · 2020Article
- COVID-19 hypothesis: Activated protein C for therapy of virus-induced pathologic thromboinflammation.Research and practice in thrombosis and haemostasis · 2020Article
- A novel myeloid cell in murine spleen defined through gene profiling.Journal of cellular and molecular medicine · 2019Article
- Article
- Activated Protein C in Cutaneous Wound Healing: From Bench to Bedside.International journal of molecular sciences · 2019Review
- Coagulopathies and inflammatory diseases: '…glimpse of a Snark'.Current opinion in immunology · 2018Review
- Regulation of immune cell signaling by activated protein C.Journal of leukocyte biology · 2018Review
- PAR1 biased signaling is required for activated protein C in vivo benefits in sepsis and stroke.Blood · 2018Article
- Activated protein C protects from GvHD via PAR2/PAR3 signalling in regulatory T-cells.Nature communications · 2017Article
- Impact of thrombosis on pulmonary endothelial injury and repair following sepsis.American journal of physiology. Lung cellular and molecular physiology · 2017Review
- 2016 Scientific Sessions Sol Sherry Distinguished Lecturer in Thrombosis: Thrombotic Stroke: Neuroprotective Therapy by Recombinant-Activated Protein C.Arteriosclerosis, thrombosis, and vascular biology · 2016Review
- Protein C receptor (PROCR) is a negative regulator of Th17 pathogenicity.The Journal of experimental medicine · 2016Article
- Protease-activated receptors in hemostasis.Blood · 2016Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Activated protein C (aPC) therapy reduces mortality in adult patients with severe sepsis. In mouse endotoxemia and sepsis models, mortality reduction requires the cell signaling function of aPC, mediated through protease-activated receptor-1 (PAR1) and endothelial protein C receptor (EPCR; also known as Procr). Candidate cellular targets of aPC include vascular endothelial cells and leukocytes. Here, we show that expression of EPCR and PAR1 on hematopoietic cells is required in mice for an aPC variant that mediates full cell signaling activity but only minimal anticoagulant function (5A-aPC) to reduce the mortality of endotoxemia. Expression of EPCR in mature murine immune cells was limited to a subset of CD8+ conventional dendritic cells. Adoptive transfer of splenic CD11chiPDCA-1- dendritic cells from wild-type mice into animals with hematopoietic EPCR deficiency restored the therapeutic efficacy of aPC, whereas transfer of EPCR-deficient CD11chi dendritic cells or wild-type CD11chi dendritic cells depleted of EPCR+ cells did not. In addition, 5A-aPC inhibited the inflammatory response of conventional dendritic cells independent of EPCR and suppressed IFN-gamma production by natural killer-like dendritic cells. These data reveal an essential role for EPCR and PAR1 on hematopoietic cells, identify EPCR-expressing dendritic immune cells as a critical target of aPC therapy, and document EPCR-independent antiinflammatory effects of aPC on innate immune cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.