ArticleInternational journal of molecular sciences2021
Efficient Neutrophil Activation Requires Two Simultaneous Activating Stimuli.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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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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Who cites it
33 citing papers in PubMed, 49 citations in OpenAlex.
- Trial
- Human Neutrophils Produce De Novo Thyroid Hormones Mediated by the Induction of the Oxidative Burst.Biomolecules · 2026Article
- Formyl peptide receptor 1 agonism selectively suppresses mitochondria-driven neutrophil extracellular trap formation while preserving antibacterial immunity.Molecular medicine (Cambridge, Mass.) · 2026Article
- Regulatory effects of beta-2-microglobulin on reactive oxygen species generation in polymorphonuclear cells.Scientific reports · 2026Article
- Sitagliptin Modulates Functional and Phenotypic Properties of Human Neutrophils Under Normal- and High-Glucose Conditions In Vitro.Molecules (Basel, Switzerland) · 2026Article
- Mitochondria as Inducers of Neutrophil Extracellular Traps.Inflammation · 2026Review
- Neutrophil Dynamics in Viral Infections: Drivers of Inflammation and Targets for Pro-Resolving Therapies.Journal of innate immunity · 2026Review
- Immune Delay, Beyond Immune Evasion, as a Driver of Pathogen Propagation Competence Through Neutrophil Dysregulation, to be Mitigated by Low-Frequency Electromagnetic Fields (LF-EMF).International journal of molecular sciences · 2025Review
- Closing infection pathways: Multidisciplinary disinfection measures reshape gastrointestinal surgical outcomes.World journal of gastrointestinal surgery · 2025Article
- Unexpected Role of TNFα Signaling in the Resolution of Postoperative Pain in Mice.Journal of pain research · 2025Article
- Exploring the pathogenesis and clinical implications of asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO): a narrative review.Frontiers in medicine · 2025Review
- Seminal plasma inhibits Chlamydia trachomatis infection in vitro, and may have consequences on mucosal immunity.Scientific reports · 2024Article
- Neutrophils and Anesthetic Drugs: Implications in Onco-Anesthesia.International journal of molecular sciences · 2024Review
- Secretomics reveals hormone-therapy of breast cancer may induce survival by facilitating hypercoagulation and immunomodulation in vitro.Scientific reports · 2024Article
- Synovial fluid extracellular vesicles as arthritis biomarkers: the added value of lipid-profiling and integrated omics.Extracellular vesicles and circulating nucleic acids · 2024Review
- COVID-19 PBMCs are doubly harmful, through LDN-mediated lung epithelial damage and monocytic impaired responsiveness to liveFrontiers in immunology · 2024Article
- Molecular regulation of neutrophil swarming in health and disease: Lessons from the phagocyte oxidase.iScience · 2023Review
- Heterodimerization of Chemoreceptors TAS1R3 and mGluInternational journal of molecular sciences · 2023Article
- Article
- Impact of Selected Bacterial and Viral Toll-like Receptor Agonists on the Phenotype and Function of Camel Blood Neutrophils.Veterinary sciences · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Neutrophils are abundantly present in the synovium and synovial fluid of patients suffering from arthritis. Neutrophils can be activated by a multitude of stimuli and the current dogma states that this is a two-step process, consisting of a priming step followed by an activation step. Considering that neutrophil activation occurs in an inflammatory environment, where multiple stimuli are present, we argue that a two-step process is highly unlikely. Here, we indeed demonstrate that neutrophils require simultaneous ligation of two different receptors for efficient activation. We isolated human peripheral blood neutrophils and cultured them with various combinations of stimuli (GM-CSF, fMLF, TNF, and LPS). Next, we evaluated essential neutrophil functions, including degranulation and ROS production using flow cytometry, mediator release using ELISA, NETosis by a live cell imaging method, phagocytosis by imaging flow cytometry, and extracellular vesicle (EV) release quantified by high-resolution flow cytometry. Exposure of neutrophils to any combination of stimuli, but not to single stimuli, resulted in significant degranulation, and mediator and EV release. Furthermore, ROS production increased substantially by dual stimulation, yet appeared to be more dependent on the type of stimulation than on dual stimulation. Phagocytosis was induced to its maximum capacity by a single stimulus, while NETosis was not induced by any of the used physiological stimuli. Our data indicate that neutrophil activation is tightly regulated and requires activation by two simultaneous stimuli, which is largely independent of the combination of stimuli.
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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.