Evidence map›Paper›PMID 21474822›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2011

Src phosphorylation of endothelial cell surface intercellular adhesion molecule-1 mediates neutrophil adhesion and contributes to the mechanism of lung inflammation.

Guoquan Liu, Stephen M Vogel, Xiaopei Gao, Kamran Javaid, Guochang Hu, Sergei M Danilov, Asrar B Malik, Richard D Minshall

Open access · bronzeAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.5field-weighted citation impact, top 12% 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

30 citing papers in PubMed, 54 citations in OpenAlex.

  1. Article
  2. Article
  3. Bosutinib mitigates inflammation in experimental sepsis.European journal of clinical investigation · 2025
    Article
  4. Review
  5. Review
  6. Article
  7. TNF-α-activated eNOS signaling increases leukocyte adhesion through theAmerican journal of physiology. Heart and circulatory physiology · 2021
    Article
  8. Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Endothelial cell SHP-2 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM-1-VE-cadherin interaction.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017
    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

8 authors at 1 institution in 2 countries.

Guoquan LiuDepartment of Pharmacology, University of Illinois, Chicago, IL, USA.
Stephen M Vogel
Xiaopei Gao
Kamran Javaid
Guochang Hu
Sergei M Danilov
Asrar B Malik
Richard D Minshall
Dr. M.G.R. Educational and Research Institute · IN

Funding

TRPC6 Regulation of Lung Endothelial Barrier FunctionP01HL060678 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MALIK, ASRAR B. · 2000 to 2020
$40.1M
Trpm2 Regulation of Phagocyte Bactericidal Activity and Resolution of Lung InjuryP01HL077806 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MALIK, ASRAR B. · 2005 to 2019
$27.0M
Src Regulation of Lung Endothelial Barrier FunctionR01HL071626 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MINSHALL, RICHARD D · 2003 to 2011
$2.4M
NHLBI NIH HHS P01 HL060678NHLBI NIH HHS P01 HL077806NHLBI NIH HHS P01-HL60678NHLBI NIH HHS P01-HL77806NHLBI NIH HHS R01 HL071626NHLBI NIH HHS R01-HL71626
6 · The paper itself

Abstract

objectiveThe goal of this study was to determine whether tumor necrosis factor α (TNFα)-induced Src activation and intercellular adhesion molecule-1 (ICAM-1) phosphorylation rapidly increase endothelial cell adhesivity and polymorphonuclear leukocyte (PMN) sequestration independently of de novo ICAM-1 synthesis. METHODS AND

resultsTNFα exposure of mouse lungs for 5 minutes produced a 3-fold increase in (125)I-anti-ICAM-1 monoclonal antibody (mAb) binding and (111)In oxine-labeled PMN sequestration, as well as Src activation, ICAM-1 Tyr518 phosphorylation, and phospho- Tyr518-ICAM-1 coimmunoprecipitation with actin. The response was absent in Nox2(-/-) lungs or following Src inhibition. In COS-7 cells transfected with wild-type (WT), phospho-defective (Tyr518Phe), or phospho-mimicking (Tyr518Asp) mouse ICAM-1 cDNA constructs, TNFα increased the B(max) of YN1/1.7.4 anti-ICAM-1 mAb binding to WT-ICAM-1 but not to Tyr518Phe-ICAM-1, indicating increased binding avidity secondary to ICAM-1 phosphorylation. This effect was mimicked by expression of the Tyr518Asp-ICAM-1 mutant. TNFα also increased the staining intensity and cell surface clustering of YN1/1.7.4 mAb-labeled WT-ICAM-1 that colocalized with F-actin, which was not observed with Tyr518Phe-ICAM-1 but was recapitulated with Tyr518Asp-ICAM-1. Finally, overexpression of ICAM-1 in mouse lungs significantly increased lipopolysaccharide-induced transvascular albumin leakage and bronchoalveolar lavage PMN counts at 2 and 24 hours after lipopolysaccharide inhalation compared with lungs expressing the Tyr518Phe ICAM-1 mutant.

conclusionSrc-dependent phosphorylation of endothelial cell ICAM-1 Tyr518 induces PMN adhesion by promoting ICAM-1 clustering, which we propose mediates rapid-phase lung vascular accumulation of PMNs during inflammation.

Indexed as

AnimalsCell AdhesionChlorocebus aethiopsCOS CellsHumansIntercellular Adhesion Molecule-1LipopolysaccharidesMaleMembrane GlycoproteinsMiceMice, Inbred C57BLNADPH Oxidase 2NADPH OxidasesNeutrophilsPhosphatidylinositol 3-KinasesPhosphorylationCYBB protein, humanIntercellular Adhesion Molecule-1LipopolysaccharidesMembrane GlycoproteinsNADPH Oxidase 2NADPH OxidasesPhosphatidylinositol 3-KinasesProtein Kinase CProtein Kinase C zetasrc-Family KinasesTumor Necrosis Factor-alpha

Identifiers

PMID21474822
PMCPMC3548602
OpenAlexW2146049220

What OpenQuestion holds

Textmetadata
LicenceTDM
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.