ArticleThe Journal of clinical investigation2020
Local microvascular leakage promotes trafficking of activated neutrophils to remote organs.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 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.
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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
51 citing papers in PubMed, 72 citations in OpenAlex.
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- The CXCL12/CXCR4 Axis in Sepsis-Induced Acute Lung Injury: Mechanisms and Therapeutic Potential.Current issues in molecular biology · 2025Review
- Aging microvasculature: Effects on immune cell trafficking and inflammatory diseases.The Journal of experimental medicine · 2025Review
- Distinct VE-cadherin serine and tyrosine phosphorylation sites and their role for inflammation-induced vascular permeability in vivo.Cellular and molecular life sciences : CMLS · 2025Article
- In Old Mice, Exercise Induces Inflammation and Fibrosis Unless Alk5-Inhibitor and Oxytocin Are Used.Journal of cellular physiology · 2025Article
- Unraveling immunosenescence in sepsis: from cellular mechanisms to therapeutics.Cell death & disease · 2025Review
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- Immunosenescence in Sepsis: Molecular Mechanisms and Potential Therapeutic Targets.Aging and disease · 2025Review
- Chemokines in the resolution of inflammation: key players and targets for therapeutic modulation.Frontiers in immunology · 2025Review
- IRG1/ACOD1 promotes neutrophil reverse migration and alleviates local inflammation.Journal of leukocyte biology · 2024Article
- Endothelial Cell-Derived Extracellular Vesicles Promote Aberrant Neutrophil Trafficking and Subsequent Remote Lung Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Neutrophils-biology and diversity.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Review
- Myosin-1C augments endothelial secretion of von Willebrand factor by linking contractile actomyosin machinery to the plasma membrane.Blood advances · 2024Article
- Senescent endothelial cells promote pathogenic neutrophil trafficking in inflamed tissues.EMBO reports · 2024Article
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- Chemerin attracts neutrophil reverse migration by interacting with C-C motif chemokine receptor-like 2.Cell death & disease · 2024Article
- The deubiquitinase USP40 preserves endothelial integrity by targeting the heat shock protein HSP90β.Experimental & molecular medicine · 2024Article
- Csk controls leukocyte extravasation via local regulation of Src family kinases and cortactin signaling.Frontiers in immunology · 2024Article
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Increased microvascular permeability to plasma proteins and neutrophil emigration are hallmarks of innate immunity and key features of numerous inflammatory disorders. Although neutrophils can promote microvascular leakage, the impact of vascular permeability on neutrophil trafficking is unknown. Here, through the application of confocal intravital microscopy, we report that vascular permeability-enhancing stimuli caused a significant frequency of neutrophil reverse transendothelial cell migration (rTEM). Furthermore, mice with a selective defect in microvascular permeability enhancement (VEC-Y685F-ki) showed reduced incidence of neutrophil rTEM. Mechanistically, elevated vascular leakage promoted movement of interstitial chemokines into the bloodstream, a response that supported abluminal-to-luminal neutrophil TEM. Through development of an in vivo cell labeling method we provide direct evidence for the systemic dissemination of rTEM neutrophils, and showed them to exhibit an activated phenotype and be capable of trafficking to the lungs where their presence was aligned with regions of vascular injury. Collectively, we demonstrate that increased microvascular leakage reverses the localization of directional cues across venular walls, thus causing neutrophils engaged in diapedesis to reenter the systemic circulation. This cascade of events offers a mechanism to explain how local tissue inflammation and vascular permeability can induce downstream pathological effects in remote organs, most notably in the lungs.
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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.