Evidence map›Paper›PMID 26868209›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2016

Glycosphingolipids on Human Myeloid Cells Stabilize E-Selectin-Dependent Rolling in the Multistep Leukocyte Adhesion Cascade.

Nandini Mondal, Gino Stolfa, Aristotelis Antonopoulos, Yuqi Zhu, Shuen-Shiuan Wang, Alexander Buffone, G Ekin Atilla-Gokcumen, Stuart M Haslam, Anne Dell, Sriram Neelamegham

Open access · bronzeAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2016. 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
4.0field-weighted citation impact, top 7% 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, 37 citations in OpenAlex.

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  15. Proteoglycans as Mediators of Cancer Tissue Mechanics.Frontiers in cell and developmental biology · 2020
    Review
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  18. I-branched carbohydrates as emerging effectors of malignant progression.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
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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

10 authors at 1 institution in 1 country.

Nandini MondalFrom the Department of Chemical and Biological Engineering (N.M., G.S., Y.Z., S.-S.W., A.B., S.N.), Department of Chemistry (G.E.A.-G.), and The NY State Center for Excellence in Bioinformatics and Life Sciences (S.N.), State University of New York, Buffalo; and Department of Life Sciences, Imperial College London, London, UK (A.A., S.M.H., A.D.).
Gino StolfaFrom the Department of Chemical and Biological Engineering (N.M., G.S., Y.Z., S.-S.W., A.B., S.N.), Department of Chemistry (G.E.A.-G.), and The NY State Center for Excellence in Bioinformatics and Life Sciences (S.N.), State University of New York, Buffalo; and Department of Life Sciences, Imperial College London, London, UK (A.A., S.M.H., A.D.).
Aristotelis AntonopoulosFrom the Department of Chemical and Biological Engineering (N.M., G.S., Y.Z., S.-S.W., A.B., S.N.), Department of Chemistry (G.E.A.-G.), and The NY State Center for Excellence in Bioinformatics and Life Sciences (S.N.), State University of New York, Buffalo; and Department of Life Sciences, Imperial College London, London, UK (A.A., S.M.H., A.D.).
Yuqi ZhuFrom the Department of Chemical and Biological Engineering (N.M., G.S., Y.Z., S.-S.W., A.B., S.N.), Department of Chemistry (G.E.A.-G.), and The NY State Center for Excellence in Bioinformatics and Life Sciences (S.N.), State University of New York, Buffalo; and Department of Life Sciences, Imperial College London, London, UK (A.A., S.M.H., A.D.).
Shuen-Shiuan WangFrom the Department of Chemical and Biological Engineering (N.M., G.S., Y.Z., S.-S.W., A.B., S.N.), Department of Chemistry (G.E.A.-G.), and The NY State Center for Excellence in Bioinformatics and Life Sciences (S.N.), State University of New York, Buffalo; and Department of Life Sciences, Imperial College London, London, UK (A.A., S.M.H., A.D.).
Alexander BuffoneFrom the Department of Chemical and Biological Engineering (N.M., G.S., Y.Z., S.-S.W., A.B., S.N.), Department of Chemistry (G.E.A.-G.), and The NY State Center for Excellence in Bioinformatics and Life Sciences (S.N.), State University of New York, Buffalo; and Department of Life Sciences, Imperial College London, London, UK (A.A., S.M.H., A.D.).
G Ekin Atilla-GokcumenFrom the Department of Chemical and Biological Engineering (N.M., G.S., Y.Z., S.-S.W., A.B., S.N.), Department of Chemistry (G.E.A.-G.), and The NY State Center for Excellence in Bioinformatics and Life Sciences (S.N.), State University of New York, Buffalo; and Department of Life Sciences, Imperial College London, London, UK (A.A., S.M.H., A.D.).
Stuart M HaslamFrom the Department of Chemical and Biological Engineering (N.M., G.S., Y.Z., S.-S.W., A.B., S.N.), Department of Chemistry (G.E.A.-G.), and The NY State Center for Excellence in Bioinformatics and Life Sciences (S.N.), State University of New York, Buffalo; and Department of Life Sciences, Imperial College London, London, UK (A.A., S.M.H., A.D.).
Anne DellFrom the Department of Chemical and Biological Engineering (N.M., G.S., Y.Z., S.-S.W., A.B., S.N.), Department of Chemistry (G.E.A.-G.), and The NY State Center for Excellence in Bioinformatics and Life Sciences (S.N.), State University of New York, Buffalo; and Department of Life Sciences, Imperial College London, London, UK (A.A., S.M.H., A.D.).
Sriram NeelameghamFrom the Department of Chemical and Biological Engineering (N.M., G.S., Y.Z., S.-S.W., A.B., S.N.), Department of Chemistry (G.E.A.-G.), and The NY State Center for Excellence in Bioinformatics and Life Sciences (S.N.), State University of New York, Buffalo; and Department of Life Sciences, Imperial College London, London, UK (A.A., S.M.H., A.D.). neel@buffalo.edu.
Imperial College London · GB

Funding

Systems Biology of GlycosylationR01HL103411 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI NEELAMEGHAM, SRIRAM · 2011 to 2025
$7.1M
SELECTIN MEDIATED CELL ADHESION UNDER HYDRODYNAMIC SHEARR01HL063014 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI NEELAMEGHAM, SRIRAM · 2001 to 2014
$3.0M
Biotechnology and Biological Sciences Research Council BB/K016164/1NHLBI NIH HHS HL103411NHLBI NIH HHS HL63014NHLBI NIH HHS R01 HL063014NHLBI NIH HHS R01 HL103411
6 · The paper itself

Abstract

objectiveRecent studies suggest that the E-selectin ligands expressed on human leukocytes may differ from those in other species, particularly mice. To elaborate on this, we evaluated the impact of glycosphingolipids expressed on human myeloid cells in regulating E-selectin-mediated cell adhesion. APPROACH AND

resultsA series of modified human cell lines and primary neutrophils were created by targeting UDP-Glucose Ceramide Glucosyltransferase using either lentivirus-delivered shRNA or CRISPR-Cas9-based genome editing. Enzymology and mass spectrometry confirm that the modified cells had reduced or abolished glucosylceramide biosynthesis. Glycomics profiling showed that UDP-Glucose Ceramide Glucosyltransferase disruption also increased prevalence of bisecting N-glycans and reduced overall sialoglycan expression on leukocyte N- and O-glycans. Microfluidics-based flow chamber studies demonstrated that both the UDP-Glucose Ceramide Glucosyltransferase knockouts and knockdowns display ≈60% reduction in leukocyte rolling and firm adhesion on E-selectin bearing stimulated endothelial cells, without altering cell adhesion to P-selectin. Consistent with the concept that the glycosphingolipids support slow rolling and the transition to firm arrest, inhibiting UDP-Glucose Ceramide Glucosyltransferase activity resulted in frequent leukocyte detachment events, skipping motion, and reduced diapedesis across the endothelium. Cells bearing truncated O- and N-glycans also sustained cell rolling on E-selectin, although their ability to be recruited from free fluid flow was diminished.

conclusionsGlycosphingolipids likely contribute to human myeloid cell adhesion to E-selectin under fluid shear, particularly the transition of rolling cells to firm arrest.

Indexed as

Leukocyte RollingTransendothelial and Transepithelial MigrationAnimalsCell AdhesionCRISPR-Cas SystemsEndothelial CellsE-SelectinFemaleGlucosyltransferasesGlycomicsGlycosphingolipidsHEK293 CellsHL-60 CellsHumansMaleMiceceramide glucosyltransferaseE-SelectinGlucosyltransferasesGlycosphingolipidsPronaseSELE protein, humancell adhesion moleculeendothelial cellflow shear stressinflammationleukocyte

Identifiers

PMID26868209
PMCPMC5567847
OpenAlexW2256457372

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.