ArticleJournal of leukocyte biology2019
Tissue-type plasminogen activator neutralizes LPS but not protease-activated receptor-mediated inflammatory responses to plasmin.
Article in Journal of leukocyte biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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
18 citing papers in PubMed, 22 citations in OpenAlex.
- 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
- Review
- Tissue-plasminogen activator effects on the phenotype of splenic myeloid cells in acute inflammation.Journal of inflammation (London, England) · 2024Article
- 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
- A Soluble PrPJournal of immunology (Baltimore, Md. : 1950) · 2022Article
- Roles of the tissue-type plasminogen activator in immune response.Cellular immunology · 2022Review
- BCI, an inhibitor of the DUSP1 and DUSP6 dual specificity phosphatases, enhances P2X7 receptor expression in neuroblastoma cells.Frontiers in cell and developmental biology · 2022Article
- Plasminogen activator receptor assemblies in cell signaling, innate immunity, and inflammation.American journal of physiology. Cell physiology · 2021Review
- Enzymatically Inactive Tissue-Type Plasminogen Activator Reverses Disease Progression in the Dextran Sulfate Sodium Mouse Model of Inflammatory Bowel Disease.The American journal of pathology · 2021Article
- Using antifibrinolytics to tackle neuroinflammation.Neural regeneration research · 2020Review
- Empty mesoporous silica particles significantly delay disease progression and extend survival in a mouse model of ALS.Scientific reports · 2020Article
- The multifaceted role of plasminogen in inflammation.Cellular signalling · 2020Review
- Functions of the plasminogen receptor Plg-RJournal of thrombosis and haemostasis : JTH · 2020Review
- Perspective on fibrinolytic therapy in COVID-19: the potential of inhalation therapy against suppressed-fibrinolytic-type DIC.Journal of intensive care · 2020Article
- Fibrinolysis protease receptors promote activation of astrocytes to express pro-inflammatory cytokines.Journal of neuroinflammation · 2019Article
- Tissue-type plasminogen activator selectively inhibits multiple toll-like receptors in CSF-1-differentiated macrophages.PloS one · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
Tissue-type plasminogen activator (tPA) activates fibrinolysis and also suppresses innate immune system responses to LPS in bone marrow-derived macrophages (BMDMs) and in vivo in mice. The objective of this study was to assess the activity of tPA as a regulator of macrophage physiology in the presence of plasmin. Enzymatically active and enzymatically inactive (EI) tPA appeared to comprehensively block the response to LPS in BMDMs, including expression of proinflammatory cytokines such as TNF-α and IL-1β and anti-inflammatory cytokines such as IL-10 and IL-1 receptor antagonist. The activity of EI-tPA as an LPS response modifier was conserved in the presence of plasminogen. By contrast, in BMDMs treated with tPA and plasminogen or preactivated plasmin, in the presence or absence of LPS, increased proinflammatory cytokine expression was observed and tPA failed to reverse the response. Plasmin independently activated NF-κB, ERK1/2, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase in BMDMs, which is characteristic of proinflammatory stimuli. Plasmin-induced cytokine expression was blocked by ε-aminocaproic acid, aprotinin, and inhibitors of the known plasmin substrate, Protease-activated receptor-1 (PAR-1), but not by N-methyl-d-aspartate receptor inhibitor, which blocks the effects of tPA on macrophages. Cytokine expression by BMDMs treated with the PAR-1 agonist, TFLLR, was not inhibited by EI-tPA, possibly explaining why EI-tPA does not inhibit macrophage responses to plasmin and providing evidence for specificity in the ability of tPA to oppose proinflammatory stimuli. Regulation of innate immunity by the fibrinolysis system may reflect the nature of the stimulus and a balance between the potentially opposing activities of tPA and plasmin.
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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.