Evidence map›Paper›PMID 23447687›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2013

Class I phosphoinositide-3-kinases and SRC kinases play a nonredundant role in regulation of adhesion-independent and -dependent neutrophil reactive oxygen species generation.

Laura Fumagalli, Carlo C Campa, Giulia Germena, Clifford A Lowell, Emilio Hirsch, Giorgio Berton

Abstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

23 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. A Review of Phosphocreatine 3 Kinase δ Subtype (PI3Kδ) and Its Inhibitors in Malignancy.Medical science monitor : international medical journal of experimental and clinical research · 2021
    Review
  8. Article
  9. Article
  10. Review
  11. Frontiers in immunology · 2020
    Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
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

6 authors at 3 institutions in 2 countries.

Laura FumagalliSection of General Pathology, Department of Pathology and Diagnostics, University of Verona, Verona 37134, Italy.
Carlo C Campa
Giulia Germena
Clifford A Lowell
Emilio Hirsch
Giorgio Berton
University of Turin · ITUniversity of Verona · ITUniversity of San Francisco · US

Funding

Mechanisms of Neutrophil ActivationR01AI065495 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LOWELL, CLIFFORD A · 2005 to 2017
$3.7M
Signaling by Cytoplasmic Tyrosine Kinases in LeukocytesR01AI068150 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LOWELL, CLIFFORD A · 2006 to 2016
$3.4M
NIAID NIH HHS R01 AI065495NIAID NIH HHS R01 AI068150
6 · The paper itself

Abstract

Chemoattractant-induced reactive oxygen species (ROS) generation by adherent neutrophils occurs in two phases: the first is very rapid and transient, and the second one is delayed and lasts up to 30-40 min. We examined the role of phosphoinositide 3-kinases (PI3Ks) and Src-family kinases (SFKs) in these responses using human neutrophils treated with inhibitory compounds or murine neutrophils deficient of PI3Kγ or Hck, Fgr, and Lyn. Our studies show that PI3Kγ is indispensable for the early, fMLF-induced ROS generation and AKT and ERK phosphorylation, but is dispensable for the late response to fMLF. Additionally, the response to TNF, an agonist triggering only the delayed phase of ROS generation, was also unaffected in PI3Kγ-deficient neutrophils. In contrast, inhibition of SFKs by a selective inhibitor in human, or SFK deficiency in murine, neutrophils resulted in the inhibition of both the early and late phase of ROS generation, without affecting the early phase of AKT phosphorylation, but inhibiting the late one. Selective inhibitors of PI3Kα and PI3Kδ markedly reduced both the early and late response to fMLF and TNF in human neutrophils. These findings suggest that class IA PI3Ks may be activated by PI3Kγ via Ras in the early phase of the response and by SFKs in the late phase. The evidence that inhibition of SFKs in human, or SFK deficiency in murine, neutrophils results in suppression of Vav phosphorylation at all time points of the response to fMLF or TNF suggests that SFKs are indispensable for Vav phosphorylation.

Indexed as

AnimalsCell AdhesionEnzyme ActivationExtracellular Signal-Regulated MAP KinasesHumansIsoenzymesMiceNeutrophilsN-Formylmethionine Leucyl-PhenylalaninePhosphatidylinositol 3-KinasesPhosphorylationProto-Oncogene Proteins c-vavProto-Oncogene Proteins p21(ras)Reactive Oxygen Speciessrc-Family KinasesTumor Necrosis FactorsExtracellular Signal-Regulated MAP KinasesIsoenzymesN-Formylmethionine Leucyl-PhenylalanineN-formylmethionyl-leucyl-phenylalanyl-lysinePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-vavProto-Oncogene Proteins p21(ras)Reactive Oxygen Speciessrc-Family KinasesTumor Necrosis Factors

Identifiers

PMID23447687
PMCPMC4280093
OpenAlexW2149301854

What OpenQuestion holds

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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.