ArticleBlood2020
NADPH oxidase controls pulmonary neutrophil infiltration in the response to fungal cell walls by limiting LTB4.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 53 citations in OpenAlex.
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- Arachidonic acid metabolism in spinal cord injury.Journal of advanced research · 2026Review
- Fungal Infections in Disorders of Inborn Errors of Immunity.Clinical reviews in allergy & immunology · 2026Review
- The Nox2 NADPH oxidase regulates neutrophilic inflammation in the oral cavity.Mucosal immunology · 2026Article
- Arachidonic acid availability controls neutrophil swarm initiation and scaling.bioRxiv : the preprint server for biology · 2026Article
- The type 1 and type 3 immune responses underlying the tissue inflammation associated with NOX2 deficiency.Frontiers in immunology · 2026Review
- Targeted RNA Therapy Reprograms Fibrotic Macrophages to Reverse Pulmonary Fibrosis.Theranostics · 2026Article
- A case report of a patient with chronic granulomatous disease complicated by invasive aspergillosis and disseminatedFrontiers in medicine · 2026Article
- Phagocyte NADPH Oxidase NOX2-Derived Reactive Oxygen Species in Antimicrobial Defense: Mechanisms, Regulation, and Therapeutic Potential-A Narrative Review.Antioxidants (Basel, Switzerland) · 2025Review
- Mucoricin binding to β-glucan sites on germinating Mucorales spores disrupts neutrophil swarming to promote pathogenicity.bioRxiv : the preprint server for biology · 2025Article
- Aspergillus fumigatus biology, immunopathogenicity and drug resistance.Nature reviews. Microbiology · 2025Review
- ATG5 suppresses type I IFN-dependent neutrophil effector functions during Mycobacterium tuberculosis infection in mice.Nature microbiology · 2025Article
- Investigating pulmonary neutrophil responses to inflammation in mice via flow cytometry.Journal of leukocyte biology · 2025Article
- Glucose metabolism controls oxidative burst and lipid mediator production in neutrophils upon microbial challenge.microLife · 2025Article
- Reactive oxygen species drive the aberrant immune response to aFrontiers in immunology · 2025Article
- Neutrophil ratio trajectory and the short-term outcome of perinatal hypoxic-ischemic encephalopathy.Frontiers in pediatrics · 2025Article
- Self-extinguishing relay waves enable homeostatic control of human neutrophil swarming.Developmental cell · 2024Article
- Neutrophils-biology and diversity.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Review
- A LTBiScience · 2024Article
- Beyond host defense and tissue injury: the emerging role of neutrophils in tissue repair.American journal of physiology. Cell physiology · 2024Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Leukocyte reduced NADP (NADPH) oxidase plays a key role in host defense and immune regulation. Genetic defects in NADPH oxidase result in chronic granulomatous disease (CGD), characterized by recurrent bacterial and fungal infections and aberrant inflammation. Key drivers of hyperinflammation induced by fungal cell walls in CGD are still incompletely defined. In this study, we found that CGD (CYBB-) neutrophils produced higher amounts of leukotriene B4 (LTB4) in vitro after activation with zymosan or immune complexes, compared with wild-type (WT) neutrophils. This finding correlated with increased calcium influx in CGD neutrophils, which was restrained in WT neutrophils by the electrogenic activity of NADPH oxidase. Increased LTB4 generation by CGD neutrophils was also augmented by paracrine cross talk with the LTB4 receptor BLT1. CGD neutrophils formed more numerous and larger clusters in the presence of zymosan in vitro compared with WT cells, and the effect was also LTB4- and BLT1-dependent. In zymosan-induced lung inflammation, focal neutrophil infiltrates were increased in CGD compared with WT mice and associated with higher LTB4 levels. Inhibiting LTB4 synthesis or antagonizing the BLT1 receptor after zymosan challenge reduced lung neutrophil recruitment in CGD to WT levels. Thus, LTB4 was the major driver of excessive neutrophilic lung inflammation in CGD mice in the early response to fungal cell walls, likely by a dysregulated feed-forward loop involving amplified neutrophil production of LTB4. This study identifies neutrophil LTB4 generation as a target of NADPH oxidase regulation, which could potentially be exploited therapeutically to reduce excessive inflammation in CGD.
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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.