ArticleThe Journal of clinical investigation2003
The molecular basis for adhesion-mediated suppression of reactive oxygen species generation by human neutrophils.
Article in The Journal of clinical investigation, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 80 citations in OpenAlex.
- The Reciprocal Relationship Between Cell Adhesion Molecules and Reactive Oxygen Species.Cells · 2025Review
- DOCK2 as a novel CD11c ligand in neutrophils to regulate reactive oxygen species production.Frontiers in immunology · 2025Article
- Particulate Matter-Induced Emerging Health Effects Associated with Oxidative Stress and Inflammation.Antioxidants (Basel, Switzerland) · 2024Review
- NADPH Oxidase 3: Beyond the Inner Ear.Antioxidants (Basel, Switzerland) · 2024Review
- Reactive Oxygen Species and Strategies for Antioxidant Intervention in Acute Respiratory Distress Syndrome.Antioxidants (Basel, Switzerland) · 2023Review
- Review
- Leveling Up the Controversial Role of Neutrophils in Cancer: When the Complexity Becomes Entangled.Cells · 2021Review
- The "Biological Weapons" ofFrontiers in cellular and infection microbiology · 2021Review
- Article
- Role of negative regulation of immune signaling pathways in neutrophil function.Journal of leukocyte biology · 2017Review
- Biomaterials differentially regulate Src kinases and phosphoinositide 3-kinase-γ in polymorphonuclear leukocyte primary and tertiary granule release.Biomaterials · 2015Article
- Mechanisms of interferon-γ production by neutrophils and its function during Streptococcus pneumoniae pneumonia.American journal of respiratory cell and molecular biology · 2015Article
- Human peripheral neutrophils express functional IL-21 receptors.Inflammation · 2014Article
- αCellular and molecular bioengineering · 2014Article
- Redox-relevant aspects of the extracellular matrix and its cellular contacts via integrins.Antioxidants & redox signaling · 2014Review
- Nitric oxide and redox mechanisms in the immune response.Journal of leukocyte biology · 2011Review
- The many roles of NOX2 NADPH oxidase-derived ROS in immunity.Seminars in immunopathology · 2010Review
- Regulation of TNF-induced oxygen radical production in human neutrophils: role of delta-PKC.Journal of leukocyte biology · 2010Article
- Targeting and regulation of reactive oxygen species generation by Nox family NADPH oxidases.Antioxidants & redox signaling · 2009Review
- Human neutrophils coordinate chemotaxis by differential activation of Rac1 and Rac2.Journal of immunology (Baltimore, Md. : 1950) · 2009Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Human neutrophil adherence to ECMs induces an initial inhibition of stimulated reactive oxygen species (ROS) formation, followed by an enhanced phase of oxidant production. The initial integrin-mediated suppression of ROS constitutes a mechanism to prevent inappropriate tissue damage as leukocytes migrate to inflammatory sites. The Rac2 guanosine 5'-triphosphatase (GTPase) is a critical regulatory component of the phagocyte NADPH oxidase. We show that activation of Rac2 is inhibited in adherent neutrophils, correlating with inhibition of ROS formation. Conversely, NADPH oxidase components p47 and p67 assemble normally, suggesting a specific action of adhesion on the Rac2 molecular switch. Reconstitution with activated Rac2 restored rapid NADPH oxidase activation kinetics to adherent neutrophils, establishing that inhibition was due to defective Rac2 activity. We provide evidence that integrins inhibit Rac2 activation via a membrane-associated guanine nucleotide exchange factor, likely to be Vav1. Activation of Vav1, but not its upstream activator, Syk, is suppressed by cell adhesion. Vav1 activity is inhibited due to dephosphorylation of the regulatory Tyr174 via enhanced tyrosine phosphatase activity in adherent cells. These studies identify an integrin-mediated pathway in which Vav1 is as a strong candidate for the critical regulatory point in suppression of Rac2 activation and ROS generation during inflammatory responses.
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What OpenQuestion holds
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.