ArticleProceedings of the National Academy of Sciences of the United States of America2020
ORAI1 and ORAI2 modulate murine neutrophil calcium signaling, cellular activation, and host defense.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
35 citing papers in PubMed, 49 citations in OpenAlex.
- KArchiv der Pharmazie · 2026Article
- Unify learns cellular evolution with universal multimodal embeddings.Nature communications · 2026Article
- CRAC channels as targets for immunotherapy.Current opinion in immunology · 2026Review
- Granulocyte differentiation arrest in HAX1-deficient cells, demonstrated in a new in vitro model of a certain phenotypic aspects of Kostmann disease, is caused by ineffective lipid droplet autophagy and fatty acids uptake.Cell death & disease · 2026Article
- Aging changes the mechanism that underlies JAK2 modulation of neutrophil function.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- NCX1 reverse mode promotes calcium-dependent Neutrophil Extracellular Trap formation and lung damage in chronic obstructive pulmonary disease.Nature communications · 2026Article
- Orai1 acts as a novel CaExperimental & molecular medicine · 2026Article
- Integrin activation by two independently regulated calcium-mediated pathways is required for neutrophil recruitment.Cell communication and signaling : CCS · 2026Article
- Regulation of bone immunity by metal ions: a review of mechanisms and application progress.Frontiers in immunology · 2026Review
- Review
- Potassium-Doped MnOACS nano · 2025Article
- Neutrophil CRACR2A Promotes Neutrophil Recruitment in Sterile Inflammation and Ischemic Stroke.Circulation · 2025Article
- Pathogenic and Protective Roles of Neutrophils inPathogens (Basel, Switzerland) · 2025Review
- Analysis of Store-Operated CaMethods in molecular biology (Clifton, N.J.) · 2025Article
- INTEGRIN FUNCTION IN LEUKOCYTE-MEDIATED INFLAMMATION-ACTINOPATHIES IN IMMUNE DISEASES.Transactions of the American Clinical and Climatological Association · 2025Review
- Cytosolic S100A8/A9 promotes CaeLife · 2024Article
- Membrane potential dynamics of C5a-stimulated neutrophil granulocytes.Pflugers Archiv : European journal of physiology · 2024Article
- Wound Repair and CaCells · 2024Review
- Synthetic Biology Meets CaCells · 2024Review
- Neutrophil-specific ORAI1 Calcium Channel Inhibition Reduces Pancreatitis-associated Acute Lung Injury.Function (Oxford, England) · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Calcium signals are initiated in immune cells by the process of store-operated calcium entry (SOCE), where receptor activation triggers transient calcium release from the endoplasmic reticulum, followed by opening of plasma-membrane calcium-release activated calcium (CRAC) channels. ORAI1, ORAI2, and ORAI3 are known to comprise the CRAC channel; however, the contributions of individual isoforms to neutrophil function are not well understood. Here, we show that loss of ORAI1 partially decreases calcium influx, while loss of both ORAI1 and ORAI2 completely abolishes SOCE. In other immune-cell types, loss of ORAI2 enhances SOCE. In contrast, we find that ORAI2-deficient neutrophils display decreased calcium influx, which is correlated with measurable differences in the regulation of neutrophil membrane potential via KCa3.1. Decreased SOCE in ORAI1-, ORAI2-, and ORAI1/2-deficient neutrophils impairs multiple neutrophil functions, including phagocytosis, degranulation, leukotriene, and reactive oxygen species (ROS) production, rendering ORAI1/2-deficient mice highly susceptible to staphylococcal infection. This study demonstrates that ORAI1 and ORAI2 are the primary components of the neutrophil CRAC channel and identifies subpopulations of neutrophils where cell-membrane potential functions as a rheostat to modulate the SOCE response. These findings have implications for mechanisms that modulate neutrophil function during infection, acute and chronic inflammatory conditions, and cancer.
Indexed as
Identifiers
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.