Evidence map›Paper›PMID 22328778›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2012

Intercellular adhesion molecule 1 engagement modulates sphingomyelinase and ceramide, supporting uptake of drug carriers by the vascular endothelium.

Daniel Serrano, Tridib Bhowmick, Rishi Chadha, Carmen Garnacho, Silvia Muro

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
3.2field-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

46 citing papers in PubMed, 61 citations in OpenAlex.

  1. Article
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  5. Anti-atherosclerotic therapies: Milestones, challenges, and emerging innovations.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Review
  6. Altered blood-brain barrier transport of nanotherapeutics in lysosomal storage diseases.Journal of controlled release : official journal of the Controlled Release Society · 2022
    Article
  7. Review
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  9. Macrophage ICAM-1 functions as a regulator of phagocytosis in LPS induced endotoxemia.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021
    Article
  10. Article
  11. Review
  12. Article
  13. Intertwined mechanisms define transport of anti-ICAM nanocarriers across the endothelium and brain delivery of a therapeutic enzyme.Journal of controlled release : official journal of the Controlled Release Society · 2020
    Article
  14. The Journal of pharmacology and experimental therapeutics · 2019
    Article
  15. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Daniel SerranoDepartment of Cell Biology and Molecular Genetics, Biological Sciences Graduate Program, University of Maryland, College Park, MD 20742, USA.
Tridib Bhowmick
Rishi Chadha
Carmen Garnacho
Silvia Muro
University of Maryland, College Park · US

Funding

Targeted replacement of defective lysosomal enzymes in the lung and brainR01HL098416 · NHLBI · UNIV OF MARYLAND, COLLEGE PARK · PI MURO, SILVIA · 2010 to 2020
$3.3M
NHLBI NIH HHS R01 HL098416NHLBI NIH HHS R01-HL098416
6 · The paper itself

Abstract

objectiveEngagement of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells by ICAM-1-targeted carriers induces cell adhesion molecule-mediated endocytosis, providing intraendothelial delivery of therapeutics. This pathway differs from classical endocytic mechanisms and invokes aspects of endothelial signaling during inflammation. ICAM-1 interacts with Na(+)/H(+) exchanger NHE1 during endocytosis, but it is unclear how this regulates plasmalemma and cytoskeletal changes. We studied such aspects in this work. METHODS AND

resultsWe used fluorescence and electron microscopy, inhibitors and knockout tools, cell culture, and mouse models. ICAM-1 engagement by anti-ICAM carriers induced sphingomyelin-enriched engulfment structures. Acid sphingomyelinase (ASM), an acidic enzyme that hydrolyzes sphingomyelin into ceramide (involved in plasmalemma deformability and cytoskeletal reorganization), redistributed to ICAM-1-engagement sites at ceramide-enriched areas. This induced actin stress fibers and carrier endocytosis. Inhibiting ASM impaired ceramide enrichment, engulfment structures, cytoskeletal reorganization, and carrier uptake, which was rescued by supplying this enzyme activity exogenously. Interfering with NHE1 rendered similar outcomes, suggesting that Na(+)/H(+) exchange might provide an acidic microenvironment for ASM at the plasmalemma.

conclusionsThese findings are consistent with the ability of endothelial cells to internalize relatively large ICAM- 1--targeted drug carriers and expand our knowledge on the regulation of the sphingomyelin/ceramide pathway by the vascular endothelium.

Indexed as

AnimalsCells, CulturedCeramidesDrug CarriersEndocytosisEndothelium, VascularHumansIntercellular Adhesion Molecule-1MiceMice, Inbred C57BLMicroscopy, ElectronSignal TransductionSphingomyelin PhosphodiesteraseCeramidesDrug CarriersIntercellular Adhesion Molecule-1Sphingomyelin Phosphodiesterase

Identifiers

PMID22328778
PMCPMC3331944
OpenAlexW2131614257

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.