ArticleThe Journal of physiology2012
K⁺-Cl⁻ cotransport mediates the bactericidal activity of neutrophils by regulating NADPH oxidase activation.
Article in The Journal of physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 29 citations in OpenAlex.
- Sheep erythrocyte potassium locus highlights MYADM family regulation of electroneutral potassium chloride cotransporters (KCC).BMC genomics · 2026Article
- Microbial and host innate immune factors affecting the persistence ofFrontiers in cellular and infection microbiology · 2026Review
- Prevalence and Prognostic Significance of Chloride Levels in Patients with Acute Medical Conditions: A Prospective Observational Study.Life (Basel, Switzerland) · 2025Article
- The role ofJournal of pharmaceutical analysis · 2023Review
- The formation and function of the neutrophil phagosome.Immunological reviews · 2023Review
- The erythroid K-Cl cotransport inhibitor [(dihydroindenyl)oxy]acetic acid blocks erythroid CaAmerican journal of physiology. Cell physiology · 2022Article
- Abundant Monovalent Ions as Environmental Signposts for Pathogens during Host Colonization.Infection and immunity · 2021Review
- KJournal of hematology & oncology · 2019Review
- The ZnBiochimica et biophysica acta. Molecular basis of disease · 2017Article
- An Exploration of Charge Compensating Ion Channels across the Phagocytic Vacuole of Neutrophils.Frontiers in pharmacology · 2017Article
- The LRRC8A Mediated "Swell Activated" Chloride Conductance Is Dispensable for Vacuolar Homeostasis in Neutrophils.Frontiers in pharmacology · 2017Article
- Hyperchloremia is associated with 30-day mortality in major trauma patients: a retrospective observational study.Scandinavian journal of trauma, resuscitation and emergency medicine · 2016Observational
- Association of Hyperchloremia With Hospital Mortality in Critically Ill Septic Patients.Critical care medicine · 2015Article
- Salt, chloride, bleach, and innate host defense.Journal of leukocyte biology · 2015Review
- Alkalinity of neutrophil phagocytic vacuoles is modulated by HVCN1 and has consequences for myeloperoxidase activity.PloS one · 2015Article
- Myeloperoxidase in human neutrophil host defence.Cellular microbiology · 2014Review
- Neutrophils at work.Nature immunology · 2014Review
- Chloride transport in functionally active phagosomes isolated from Human neutrophils.Free radical biology & medicine · 2012Article
- Possible association between dysnatremias and mortality during hospitalization in patients undergoing acute hemodialysis: analysis from a Peruvian retrospective cohort.Jornal brasileiro de nefrologiaArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neutrophilic phagocytosis is an essential component of innate immunity. During phagocytosis, the generation of bactericidal hypochlorous acid(HOCl) requires the substrates, Cl− and superoxide produced by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to kill the internalized pathogens. Here we show that the neutrophilic K+–Cl− cotransporter (KCC) constitutes aCl− permeation pathway and mediates the bactericidal activity by regulating NADPH oxidase activation. Dihydroindenyloxy alkanoic acid (DIOA), a KCC inhibitor, suppressed the toxin- or chemical-induced efflux of 36Cl− or 86Rb+, and diminished the production of superoxide in human and murine neutrophils. Inhibition of KCC activity or knockdown of KCC expression, in particular KCC3, reduced the phosphorylation as well as the membrane recruitment of oxidase components. Activated neutrophils displayed a significant colocalization of KCC3 and early endosomal marker, indicating that KCC3 could be localized on the phagosomes once neutrophils are activated. The NADPH oxidase activity and the phosphorylation level of oxidase component were 50% lower in the neutrophils isolated from KCC3−/− mice than in the neutrophils isolated from KCC3+/+ mice.Mortality rate after intraperitoneal challenge with Staphylococcus aureus was higher in KCC3−/− mice, and the bacterial clearance was impaired in the survivors.We conclude that, in activated neutrophil, NADPH oxidase complexes are associated with KCC3 at the plasma membrane and are internalized to form phagosomes, where KCC activity and expression level affect the production of oxidants.
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.