Evidence map›Paper›PMID 22157766›Full record

ArticleThe Journal of biological chemistry2012

NADPH oxidase is internalized by clathrin-coated pits and localizes to a Rab27A/B GTPase-regulated secretory compartment in activated macrophages.

Patrick Ejlerskov, Dan Ploug Christensen, David Beyaie, James B Burritt, Marie-Helene Paclet, Agnes Gorlach, Bo van Deurs, Frederik Vilhardt

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
0.7field-weighted citation impact, top 30% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.

  1. Pooled it
  2. Review
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  4. Review
  5. Distinct Cell-specific Roles of NOX2 and MyD88 in Epileptogenesis.Frontiers in cell and developmental biology · 2022
    Review
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  7. Article
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  16. Article
  17. Nox NADPH oxidases and the endoplasmic reticulum.Antioxidants & redox signaling · 2014
    Review
  18. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 4 countries.

Patrick EjlerskovDepartment of Cellular and Molecular Medicine, Panum Institute, Faculty of Health Sciences, University of Copenhagen, Copenhagen 2200N, Denmark.
Dan Ploug Christensen
David Beyaie
James B Burritt
Marie-Helene Paclet
Agnes Gorlach
Bo van Deurs
Frederik Vilhardt
University of Copenhagen · DKCentre National de la Recherche Scientifique · FRDeutsches Herzzentrum München · DEUniversity of Wisconsin–Stout · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Here, we report that activation of different types of tissue macrophages, including microglia, by lipopolysaccharide (LPS) or GM-CSF stimulation correlates with the quantitative redistribution of NADPH oxidase (cyt b(558)) from the plasma membrane to an intracellular stimulus-responsive storage compartment. Cryo-immunogold labeling of gp91(phox) and CeCl(3) cytochemistry showed the presence of gp91(phox) and oxidant production in numerous small (<100 nm) vesicles. Cell homogenization and sucrose gradient centrifugation in combination with transferrin-HRP/DAB ablation showed that more than half of cyt b(558) is present in fractions devoid of endosomal markers, which is supported by morphological evidence to show that the cyt b(558)-containing compartment is distinct from endosomes or biosynthetic organelles. Streptolysin-O-mediated guanosine 5'-3-O-(thio)triphosphate loading of Ra2 microglia caused exocytosis of a major complement of cyt b(558) under conditions where lysosomes or endosomes were not mobilized. We establish phagocytic particles and soluble mediators ATP, TNFα, and CD40L as physiological inducers of cyt b(558) exocytosis to the cell surface, and by shRNA knockdown, we identify Rab27A/B as positive or negative regulators of vesicular mobilization to the phagosome or the cell surface, respectively. Exocytosis was followed by clathrin-dependent internalization of cyt b(558), which could be blocked by a dominant negative mutant of the clathrin-coated pit-associated protein Eps15. Re-internalized cyt b(558) did not reach lysosomes but associated with recycling endosomes and undefined vesicular elements. In conclusion, cyt b(558) depends on clathrin for internalization, and in activated macrophages NADPH oxidase occupies a Rab27A/B-regulated secretory compartment, which allows rapid agonist-induced redistribution of superoxide production in the cell.

Indexed as

Adenosine TriphosphateAnimalsCalcium-Binding ProteinsCD40 LigandCells, CulturedClathrinClathrin-Coated VesiclesCytochrome b GroupEndosomesExocytosisIntracellular Signaling Peptides and ProteinsMacrophage ActivationMacrophagesMembrane GlycoproteinsMicrogliaNADPH Oxidase 2Adenosine TriphosphateCalcium-Binding ProteinsCD40 LigandClathrinCybb protein, ratCytochrome b GroupEps15 protein, ratIntracellular Signaling Peptides and ProteinsMembrane GlycoproteinsNADPH Oxidase 2NADPH OxidasesRab27a protein, ratRab27b protein, ratrab27 GTP-Binding Proteinsrab GTP-Binding ProteinsSuperoxidesTumor Necrosis Factor-alpha

Identifiers

PMID22157766
PMCPMC3281610
OpenAlexW2031874893

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.