ArticleBlood2017
Tissue-type plasminogen activator regulates macrophage activation and innate immunity.
Article in Blood, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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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.
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Who cites it
48 citing papers in PubMed, 66 citations in OpenAlex.
- N-Methyl-D-aspartate receptors: structure, signaling and roles in atherosclerosis.Journal of translational medicine · 2026Review
- LMO7 Suppresses Tumor-Associated Macrophage Phagocytosis of Tumor Cells Through Degradation of LRP1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Endothelial tPA-dependent recruitment of microglia to vessels protects the blood-brain barrier after stroke.Fluids and barriers of the CNS · 2026Article
- The low-density lipoprotein receptor-related protein-1 (LRP1) in Schwann cells controls mitochondria homeostasis in peripheral nerves.Progress in neurobiology · 2025Article
- Nebulized alteplase in coronavirus disease 2019 pneumonia: a case series.Journal of medical case reports · 2024Article
- The emerging role of tranexamic acid and its principal target, plasminogen, in skeletal health.Acta pharmaceutica Sinica. B · 2024Review
- The Janus face of endogenous neuronal tPA: promoting self-protection and worsening the death of neighboring neurons.Cell death & disease · 2024Article
- Review
- Tissue-plasminogen activator effects on the phenotype of splenic myeloid cells in acute inflammation.Journal of inflammation (London, England) · 2024Article
- Prospective Application of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Disseminated Intravascular Coagulation.International journal of nanomedicine · 2024Review
- Crosstalk between the plasminogen/plasmin system and inflammation resolution.Journal of thrombosis and haemostasis : JTH · 2023Review
- An LRP1-binding motif in cellular prion protein replicates cell-signaling activities of the full-length protein.JCI insight · 2023Article
- Macrophage Function Modulated by tPA Signaling in Mouse Experimental Kidney Disease Models.International journal of molecular sciences · 2023Review
- Fibrinolysis Shutdown and Hypofibrinolysis Are Not Synonymous Terms: The Clinical Significance of Differentiating Low Fibrinolytic States.Seminars in thrombosis and hemostasis · 2023Review
- An antibody that targets cell-surface glucose-regulated protein-78 inhibits expression of inflammatory cytokines and plasminogen activator inhibitors by macrophages.Journal of cellular biochemistry · 2023Article
- All tangled up: interactions of the fibrinolytic and innate immune systems.Frontiers in medicine · 2023Review
- von Willebrand factor links primary hemostasis to innate immunity.Nature communications · 2022Article
- The LRP1/CD91 ligands, tissue-type plasminogen activator, αScientific reports · 2022Article
- Targeting NMDA Receptors at the Neurovascular Unit: Past and Future Treatments for Central Nervous System Diseases.International journal of molecular sciences · 2022Review
- Balancing Microthrombosis and Inflammation via Injectable Protein Hydrogel for Inflammatory Bowel Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Tissue-type plasminogen activator (tPA) is the major intravascular activator of fibrinolysis and a ligand for receptors involved in cell signaling. In cultured macrophages, tPA inhibits the response to lipopolysaccharide (LPS) by a pathway that apparently requires low-density lipoprotein receptor-related protein-1 (LRP1). Herein, we show that the mechanism by which tPA neutralizes LPS involves rapid reversal of IκBα phosphorylation. tPA independently induced transient IκBα phosphorylation and extracellular signal-regulated kinase 1/2 (ERK1/2) activation in macrophages; however, these events did not trigger inflammatory mediator expression. The tPA signaling response was distinguished from the signature of signaling events elicited by proinflammatory LRP1 ligands, such as receptor-associated protein (RAP), which included sustained IκBα phosphorylation and activation of all 3 MAP kinases (ERK1/2, c-Jun kinase, and p38 MAP kinase). Enzymatically active and inactive tPA demonstrated similar immune modulatory activity. Intravascular administration of enzymatically inactive tPA in mice blocked the toxicity of LPS. In mice not treated with exogenous tPA, the plasma concentration of endogenous tPA increased 3-fold in response to LPS, to 116 ± 15 pM, but remained below the approximate threshold for eliciting anti-inflammatory cell signaling in macrophages (∼2.0 nM). This threshold is readily achieved in patients when tPA is administered therapeutically for stroke. In addition to LRP1, we demonstrate that the
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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.