Evidence map›Paper›PMID 18794338›Full record

ArticleThe Journal of experimental medicine2008

PSGL-1 engagement by E-selectin signals through Src kinase Fgr and ITAM adapters DAP12 and FcR gamma to induce slow leukocyte rolling.

Alexander Zarbock, Clare L Abram, Matthias Hundt, Amnon Altman, Clifford A Lowell, Klaus Ley

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed
8.4field-weighted citation impact, top 2% 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

112 citing papers in PubMed, 193 citations in OpenAlex.

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  3. [Force-regulation mechanism of E-selectin mediated adhesion and activation of MDA-MB-231 cells under fluid shear stress].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2026
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52 more citing papers are in PubMed but not listed here.

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 3 countries.

Alexander ZarbockRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA.
Clare L Abram
Matthias Hundt
Amnon Altman
Clifford A Lowell
Klaus Ley
La Jolla Institute for Immunology · USUniversity of California, San Francisco · USCardiovascular Research Center · BR

Funding

ROLE OF INFLAMMATION IN PULMONARY INJURYP01HL073361 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI MEHRAD, BORNA · 2004 to 2008
$8.0M
Mechanisms of Neutrophil ActivationR01AI065495 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LOWELL, CLIFFORD A · 2005 to 2017
$3.7M
NHLBI NIH HHS HL73361NHLBI NIH HHS P01 HL073361NIAID NIH HHS AI065495NIAID NIH HHS R01 AI065495
6 · The paper itself

Abstract

E-selectin binding to P-selectin glycoprotein ligand-1 (PSGL-1) can activate the beta(2) integrin lymphocyte function-associated antigen-1 by signaling through spleen tyrosine kinase (Syk). This signaling is independent of G alpha(i)-protein-coupled receptors, results in slow rolling, and promotes neutrophil recruitment to sites of inflammation. However, the signaling pathways linking E-selectin engagement of PSGL-1 to Syk activation are unknown. To test the role of Src family kinases and immunoreceptor tyrosine-based activating motif (ITAM)-containing adaptor proteins, we used different gene-deficient mice in flow chamber, intravital microscopy, and peritonitis studies. E-selectin-mediated phosphorylation of Syk and slow rolling was abolished in neutrophils from fgr(-/-) or hck(-/-) lyn(-/-) fgr(-/-) mice. Neutrophils from Tyrobp(-/-) Fcrg(-/-) mice lacking both DAP12 and FcRgamma were incapable of sustaining slow neutrophil rolling on E-selectin and intercellular adhesion molecule-1 and were unable to phosphorylate Syk and p38 MAPK. This defect was confirmed in vivo by using mixed chimeric mice. G alpha(i)-independent neutrophil recruitment into the inflamed peritoneal cavity was sharply suppressed in Tyrobp(-/-) Fcrg(-/-) mice. Our data demonstrate that an ITAM-dependent pathway involving the Src-family kinase Fgr and the ITAM-containing adaptor proteins DAP12 and FcRgamma is involved in the initial signaling events downstream of PSGL-1 that are required to initiate neutrophil slow rolling.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsEnzyme ActivationE-SelectinGTP-Binding Protein alpha Subunits, Gi-GoIntracellular Signaling Peptides and ProteinsLeukocyte RollingMembrane GlycoproteinsMiceMice, Inbred C57BLMice, KnockoutNeutrophilsProtein-Tyrosine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-hckReceptors, IgGAdaptor Proteins, Signal TransducingE-SelectinGTP-Binding Protein alpha Subunits, Gi-GoHck protein, mouseIntracellular Signaling Peptides and Proteinslyn protein-tyrosine kinaseMembrane GlycoproteinsProtein-Tyrosine KinasesProto-Oncogene Proteinsproto-oncogene proteins c-fgrProto-Oncogene Proteins c-hckP-selectin ligand proteinReceptors, IgGsrc-Family KinasesSyk KinaseSyk protein, mouseTyrobp protein, mouse

Identifiers

PMID18794338
PMCPMC2556779
OpenAlexW2128793357

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.