Evidence map›Paper›PMID 22791291›Full record

ArticleBlood2012

Inactivation of heparan sulfate 2-O-sulfotransferase accentuates neutrophil infiltration during acute inflammation in mice.

Jakob Axelsson, Ding Xu, Bit Na Kang, Julia K Nussbacher, Tracy M Handel, Klaus Ley, P Sriramarao, Jeffrey D Esko

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

61 citing papers in PubMed, 91 citations in OpenAlex.

  1. Article
  2. Review
  3. Heparan Sulfate Proteoglycans in Immunity.Proteoglycan research · 2026
    Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Using heparan sulfate octadecasaccharide (18-mer) as a multi-target agent to protect against sepsis.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Increased capillary stalling is associated with endothelial glycocalyx loss in subcortical vascular dementia.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022
    Article
  17. Review
  18. Article
  19. Review
  20. Article

1 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

8 authors at 4 institutions in 1 country.

Jakob AxelssonDepartment of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093, USA.
Ding Xu
Bit Na Kang
Julia K Nussbacher
Tracy M Handel
Klaus Ley
P Sriramarao
Jeffrey D Esko
University of California, San Diego · USUniversity of Minnesota · USLa Jolla Institute for Immunology · USUniversity of Montana · US

Funding

TRM and airway inflammation and remodelingU19AI070535 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROIDE, DAVID H · 2006 to 2025
$34.2M
Siglec Modulation of Inflammation in Humans and MiceP01HL057345 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI VARKI, NISSI MARY · 1997 to 2012
$24.1M
Siglec Modulation of Inflammatory ResponsesP01HL107150 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LE, DZUNG T · 2011 to 2017
$18.0M
STRUCTURE OF MACROPHAGE CHEMOTACTIC ACTIVATING PROTEINSR01AI037113 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HANDEL, TRACY M · 1995 to 2015
$5.2M
Biomarkers of Inflammation and Vaso-occlusion in Sickle Cell DiseaseR01HL111969 · NHLBI · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI FIELD, JOSHUA JEFFREY, LINDEN, JOEL M. · 2012 to 2016
$4.0M
Leukocyte Adhesion in Allergic InflammationR01AI035796 · NIAID · UNIVERSITY OF MINNESOTA · PI SRIRAMARAO, P. · 2000 to 2009
$3.6M
NHLBI NIH HHS P01 HL057345NHLBI NIH HHS P01 HL107150NHLBI NIH HHS P01 HL57345NHLBI NIH HHS R01 HL 111969NHLBI NIH HHS R01 HL111969NIAID NIH HHS R01 AI035796NIAID NIH HHS R01 AI037113NIAID NIH HHS R01 AI37113NIAID NIH HHS U19 AI070535
6 · The paper itself

Abstract

Neutrophil recruitment and extravasation at sites of inflammation provide a mechanism for host defense. We showed previously that heparan sulfate, a type of sulfated glycosaminoglycan, facilitates neutrophil recruitment based on the reduction of neutrophil infiltration in mice in which the overall sulfation of the chains was reduced by selective inactivation of N-acetylglucosamine N-deacetylase-N-sulfotransferase (Ndst1) in endothelial cells. Here we show that inactivation of uronyl 2-O-sulfotransferase in endothelial cells (Hs2st), an enzyme that acts downstream from Ndst1, results in enhanced neutrophil recruitment in several models of acute inflammation. Enhanced neutrophil infiltration resulted in part from reduced rolling velocity under flow both in vivo and in vitro, which correlated with stronger binding of neutrophil L-selectin to mutant endothelial cells. Hs2st-deficient endothelial cells also displayed a striking increase in binding of IL-8 and macrophage inflammatory protein-2. The enhanced binding of these mediators of neutrophil recruitment resulted from a change in heparan sulfate structure caused by increased N-sulfation and 6-O-sulfation of glucosamine units in response to the decrease in 2-O-sulfation of uronic acid residues. This gain-of-function phenotype provides formidable evidence demonstrating the importance of endothelial heparan sulfate in inflammation and suggests a novel enzyme target for enhancing the innate immune response.

Indexed as

Gene SilencingNeutrophil InfiltrationAnimalsCells, CulturedChemokinesEndothelial CellsHeparan SulfateInflammationL-SelectinMaleMiceMice, Inbred C57BLNeutrophilsPeritonitisSulfotransferasesThioglycolatesChemokinesHeparan Sulfateheparan-sulfate 2-sulfotransferaseL-SelectinSulfotransferasesThioglycolates

Identifiers

PMID22791291
PMCPMC3429312
OpenAlexW2056692572

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.