ArticleInternational journal of molecular sciences2020
Recombinant Tissue Plasminogen Activator (r-tPA) Induces In-Vitro Human Neutrophil Migration via Low Density Lipoprotein Receptor-Related Protein 1 (LRP-1).
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Effects of predictive nursing intervention on cognitive impairment and neurological function in ischemic stroke patients.Brain and behavior · 2023Trial
- Construction of an In Vitro Blood-Brain Barrier Micro-Organoid Model Using Decellularized Squid Mantle Scaffold Film.Journal of functional biomaterials · 2026Article
- Neutrophils in Myocarditis: A Focus on the Secretory and Phagocytotic Functions.Reviews in cardiovascular medicine · 2025Review
- PA System in the Pathogenesis of Ischemic Stroke.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- Asparagine Endopeptidase Inhibition Attenuates Tissue Plasminogen Activator-Induced Brain Hemorrhagic Transformation After Ischemic Stroke.CNS neuroscience & therapeutics · 2025Article
- Tissue-plasminogen activator effects on the phenotype of splenic myeloid cells in acute inflammation.Journal of inflammation (London, England) · 2024Article
- Clearance of apoptotic cells by neutrophils in inflammation and cancer.Cell death discovery · 2024Review
- Polyphenols: immunonutrients tipping the balance of immunometabolism in chronic diseases.Frontiers in immunology · 2024Review
- The role of neutrophils in tPA thrombolysis after stroke: a malicious troublemaker.Frontiers in immunology · 2024Review
- Predictive value of neutrophil to apolipoprotein A1 ratio in patients with acute ischaemic stroke.Brain communications · 2024Article
- Multi-faceted role of LRP1 in the immune system.Frontiers in immunology · 2023Review
- Double-Gene Copromoting Expression Analysis in tPA/GH Transgenic Goat Mammary Epithelial Cells and Thrombolytic Activity of tPA In Vitro.BioMed research international · 2022Article
- Neutrophil extracellular traps promote tPA-induced brain hemorrhage via cGAS in mice with stroke.Blood · 2021Article
- The Dual Role of Low-Density Lipoprotein Receptor-Related Protein 1 in Atherosclerosis.Frontiers in cardiovascular medicine · 2021Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Thrombolysis is the gold standard treatment for acute ischemic stroke. Besides its fibrinolytic role, recombinant tissue plasminogen activator (r-tPA) holds several non-fibrinolytic functions. Here, we investigated the potential role of r-tPA on human primary neutrophil migration in vitro. By means of modified Boyden chamber migration assay and checkerboard analysis we showed a dose-dependent chemotactic effect of r-TPA with a maximum effect reached by 0.03 mg/mL (0.003-1 mg/mL). Pre-incubation with MAP kinases inhibitors allowed the identification of PI3K/Akt, but not ERK1/2 as the intracellular pathway mediating the observed effects. Furthermore, by means of real-time PCR, immunocytochemistry and cytofluorimetry we demonstrated that the r-tPA receptor low density lipoprotein receptor-related protein 1 (LRP-1) is synthetized and expressed by neutrophils in response to r-tPA and TNF-α. Inhibition of LRP-1 by receptor-associated protein (RAP), prevented r-tPA-mediated F-actin polymerization, migration and signal through Akt but not ERK1/2. Lastly, also neutrophil degranulation in response to r-tPA seems to be mediated by LRP-1 under adhesion conditions. In conclusion, we show that r-tPA induces neutrophil chemotaxis through LRP-1/Akt pathway. Blunting r-tPA-mediated neutrophil activation might be beneficial as an adjuvant therapy to thrombolysis in this setting.
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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.