ArticleProceedings of the National Academy of Sciences of the United States of America2019
Plasma kallikrein modulates immune cell trafficking during neuroinflammation via PAR2 and bradykinin release.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 56 citations in OpenAlex.
- Signatures of immune reprogramming in anti-CD52 therapy of MS: markers for risk stratification and treatment response.Neurological research and practice · 2019Trial
- The proteinase-activated receptor-2 mediates protective immunity in early experimental leishmaniasis.Emerging microbes & infections · 2026Article
- The kallikrein-kinin system modulates CD4Journal of neuroinflammation · 2026Article
- Progranulin haploinsufficiency remodels the cerebral microvasculature and neurovascular unit.bioRxiv : the preprint server for biology · 2026Article
- Cross-disease LC-MS/MS plasma proteomics identifies reproducible shared and disease-enriched biomarker signatures in neurodegenerative disorders.Acta neuropathologica communications · 2026Article
- Critical role of keratinocytes and protease-activated receptor 2 in secondary lymphedema development.Clinical and translational medicine · 2026Article
- Harnessing Distinct Tissue-Resident Immune Niches via S100A9/TLR4 Improves Ketone, Lipid, and Glucose Metabolism.Endocrinology · 2025Article
- Non-classical neutrophil extracellular traps induced by PAR2-signaling proteases.Cell death & disease · 2025Article
- A New Strategy in Modulating the Protease-Activated Receptor 2 (Par2) in Autoimmune Diseases.International journal of molecular sciences · 2025Review
- Proteomic profiling of serum in cats with naturally occurring degenerative joint disease and co-morbid conditions.Frontiers in pain research (Lausanne, Switzerland) · 2025Article
- Oligodendrocyte and Myelin Pathophysiology in Multiple Sclerosis.Advances in neurobiology · 2025Review
- Pharmacogenomics of clinical response to Natalizumab in multiple sclerosis: a genome-wide multi-centric association study.Journal of neurology · 2024Article
- Bat-derived oligopeptide LE6 inhibits the contact-kinin pathway and harbors anti-thromboinflammation and stroke potential.Zoological research · 2024Article
- Delayed plasma kallikrein inhibition fosters post-stroke recovery by reducing thrombo-inflammation.Journal of neuroinflammation · 2024Article
- Par2-mediated responses in inflammation and regeneration: choosing between repair and damage.Inflammation and regeneration · 2024Review
- PARting Neuroinflammation with Protease-Activated Receptor 2 Pepducins.The Journal of pharmacology and experimental therapeutics · 2024Article
- Pharmacological targeting of coagulation factor XI attenuates experimental autoimmune encephalomyelitis in mice.Metabolic brain disease · 2023Article
- Association Between Prekallikrein and Stroke: A Mendelian Randomization Study.Journal of the American Heart Association · 2023Article
- NETs-Induced Thrombosis Impacts on Cardiovascular and Chronic Kidney Disease.Circulation research · 2023Review
- Induced Coma, Death, and Organ Transplantation: A Physiologic, Genetic, and Theological Perspective.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Blood-brain barrier (BBB) disruption and transendothelial trafficking of immune cells into the central nervous system (CNS) are pathophysiological hallmarks of neuroinflammatory disorders like multiple sclerosis (MS). Recent evidence suggests that the kallikrein-kinin and coagulation system might participate in this process. Here, we identify plasma kallikrein (KK) as a specific direct modulator of BBB integrity. Levels of plasma prekallikrein (PK), the precursor of KK, were markedly enhanced in active CNS lesions of MS patients. Deficiency or pharmacologic blockade of PK renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by a remarkable reduction of BBB disruption and CNS inflammation. In vitro analysis revealed that KK modulates endothelial cell function in a protease-activated receptor-2-dependent manner, leading to an up-regulation of the cellular adhesion molecules Intercellular Adhesion Molecule 1 and Vascular Cell Adhesion Molecule 1, thereby amplifying leukocyte trafficking. Our study demonstrates that PK is an important direct regulator of BBB integrity as a result of its protease function. Therefore, KK inhibition can decrease BBB damage and cell invasion during neuroinflammation and may offer a strategy for the treatment of MS.
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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.