ArticleThe Journal of clinical investigation2007
Neutrophil-mediated oxidative burst and host defense are controlled by a Vav-PLCgamma2 signaling axis in mice.
Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 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.
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
70 citing papers in PubMed, 123 citations in OpenAlex.
- Plasma glutamate-modulated interaction of A2AR and mGluR5 on BMDCs aggravates traumatic brain injury-induced acute lung injury.The Journal of experimental medicine · 2013Trial
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- The mechanism by which FGF23/FGFR-1 activates NOX2-ROS in vascular endothelial cells in the context of severe heat stroke-induced acute lung injury.Burns & trauma · 2025Article
- Vav family exchange factors: Potential regulator in atherosclerosis.Biochemistry and biophysics reports · 2024Review
- Synthetic Circular RNA for microRNA-1269a Suppresses Tumor Progression in Oral Squamous Cell Carcinoma.Cancers · 2024Article
- Inflammatory ER stress responses dictate the immunopathogenic progression of systemic candidiasis.The Journal of clinical investigation · 2023Article
- Conditional Knockout of Hypoxia-Inducible Factor 1-Alpha in Tumor-Infiltrating Neutrophils Protects against Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2023Article
- The Rac-GEF Tiam1 controls integrin-dependent neutrophil responses.Frontiers in immunology · 2023Article
- Dock2 generates characteristic spatiotemporal patterns of Rac activity to regulate neutrophil polarisation, migration and phagocytosis.Frontiers in immunology · 2023Article
- Myeloperoxidase: a new target for the treatment of stroke?Neural regeneration research · 2022Review
- Targeting Oxidative Stress in Septic Acute Kidney Injury: From Theory to Practice.Journal of clinical medicine · 2021Review
- Neutrophil-Dependent Immunity During Pulmonary Infections and Inflammations.Frontiers in immunology · 2021Review
- NETosis as a Pathogenic Factor for Heart Failure.Oxidative medicine and cellular longevity · 2021Review
- Yersinia pseudotuberculosis YopH targets SKAP2-dependent and independent signaling pathways to block neutrophil antimicrobial mechanisms during infection.PLoS pathogens · 2020Article
- SKAP2 is required for defense againsteLife · 2020Article
- Neutrophils as emerging therapeutic targets.Nature reviews. Drug discovery · 2020Review
- Roscovitine enhances all-Oncotarget · 2020Article
- The Regulatory Effects of Interleukin-4 Receptor Signaling on Neutrophils in Type 2 Immune Responses.Frontiers in immunology · 2019Review
- Calcium signalling and related ion channels in neutrophil recruitment and function.European journal of clinical investigation · 2018Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Oxidative burst, a critical antimicrobial mechanism of neutrophils, involves the rapid generation and release of reactive oxygen intermediates (ROIs) by the NADPH oxidase complex. Genetic mutations in an NADPH oxidase subunit, gp91 (also referred to as NOX2), are associated with chronic granulomatous disease (CGD), which is characterized by recurrent and life-threatening microbial infections. To combat such infections, ROIs are produced by neutrophils after stimulation by integrin-dependent adhesion to the ECM in conjunction with stimulation from inflammatory mediators, or microbial components containing pathogen-associated molecular patterns. In this report, we provide genetic evidence that both the Vav family of Rho GTPase guanine nucleotide exchange factors (GEFs) and phospholipase C-gamma2 (PLC-gamma2) are critical mediators of adhesion-dependent ROI production by neutrophils in mice. We also demonstrated that Vav was critically required for neutrophil-dependent host defense against systemic infection by Staphylococcus aureus and Pseudomonas aeruginosa, 2 common pathogens associated with fatal cases of hospital-acquired pneumonia. We identified a molecular pathway in which Vav GEFs linked integrin-mediated signaling with PLC-gamma2 activation, release of intracellular Ca2+ cations, and generation of diacylglycerol to control assembly of the NADPH oxidase complex and ROI production by neutrophils. Taken together, our data indicate that integrin-dependent signals generated during neutrophil adhesion contribute to the activation of NADPH oxidase by a variety of distinct effector pathways, all of which require Vav.
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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.