Evidence map›Paper›PMID 22236141›Full record

ArticleImmunology2012

Differential regulation of acid sphingomyelinase in macrophages stimulated with oxidized low-density lipoprotein (LDL) and oxidized LDL immune complexes: role in phagocytosis and cytokine release.

Jean-Philip Truman, Mohammed M Al Gadban, Kent J Smith, Russell W Jenkins, Nalini Mayroo, Gabriel Virella, Maria F Lopes-Virella, Alicja Bielawska, Yusuf A Hannun, Samar M Hammad

Open access · bronzeAbstract read
In one paragraph

Article in Immunology, 2012. 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
2.0field-weighted citation impact, top 14% 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, 60 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Acid Sphingomyelinase Deficiency: A Clinical and Immunological Perspective.International journal of molecular sciences · 2021
    Review
  8. Article
  9. Article
  10. The Messenger Apps of the cell: Extracellular Vesicles as Regulatory Messengers of Microglial Function in the CNS.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020
    Review
  11. Review
  12. Article
  13. TBC1D3 regulates the payload and biological activity of extracellular vesicles that mediate tissue repair.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Acid sphingomyelinase mediates human CD4Cell death & disease · 2017
    Review
  19. Review
  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

10 authors at 2 institutions in 1 country.

Jean-Philip TrumanDepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Mohammed M Al Gadban
Kent J Smith
Russell W Jenkins
Nalini Mayroo
Gabriel Virella
Maria F Lopes-Virella
Alicja Bielawska
Yusuf A Hannun
Samar M Hammad
Medical University of South Carolina · USRalph H. Johnson VA Medical Center · US

Funding

THE ROLE OF LACTOSYLCERAMIDE IN RENAL AGING AND DISEASEP20RR017677 · NCRR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI CROSSON, CRAIG E. · 2002 to 2011
$23.4M
SECRETED ADIPOCYTE PROTEINS, INSULIN RESISTANCE VASCULARP01HL055782 · NHLBI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI MCGEE, DANIEL L · 1996 to 2005
$8.9M
Biomarkers of Vascular Disease Progression in Type 1 Diabetes MellitusR01DK081352 · NIDDK · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI LOPES-VIRELLA, MARIA F · 2008 to 2011
$2.2M
Sphingolipid signaling induced by LDL immune complexesR01HL079274 · NHLBI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI HAMMAD, SAMAR M · 2006 to 2010
$1.6M
NCRR NIH HHS P20 RR017677NCRR NIH HHS P20 RR17677NHLBI NIH HHS HL079274NHLBI NIH HHS P01 HL055782NHLBI NIH HHS P01 HL55782NHLBI NIH HHS R01 HL079274NHLBI NIH HHS R01 HL079274-04S1NIDDK NIH HHS R01 DK081352NIDDK NIH HHS R01 DK081352-02S1
6 · The paper itself

Abstract

Oxidized low-density lipoprotein (oxLDL) and oxLDL-containing immune complexes (oxLDL-IC) contribute to the formation of lipid-laden macrophages (foam cells). Fcγ receptors mediate uptake of oxLDL-IC, whereas scavenger receptors internalize oxLDL. We have previously reported that oxLDL-IC, but not free oxLDL, activate macrophages and prolong their survival. Sphingomyelin is a major constituent of cell membranes and lipoprotein particles and acid sphingomyelinase (ASMase) hydrolyses sphingomyelin to generate the bioactive lipid ceramide. ASMase exists in two forms: lysosomal (L-ASMase) and secretory (S-ASMase). In this study we examined whether oxLDL and oxLDL-IC regulate ASMase differently, and whether ASMase mediates monocyte/macrophage activation and cytokine release. The oxLDL-IC, but not oxLDL, induced early and consistent release of catalytically active S-ASMase. The oxLDL-IC also consistently stimulated L-ASMase activity, whereas oxLDL induced a rapid transient increase in L-ASMase activity before it steadily declined below baseline. Prolonged exposure to oxLDL increased L-ASMase activity; however, activity remained significantly lower than that induced by oxLDL-IC. Further studies were aimed at defining the function of the activated ASMase. In response to oxLDL-IC, heat-shock protein 70B' (HSP70B') was up-regulated and localized with redistributed ASMase in the endosomal compartment outside the lysosome. Treatment with oxLDL-IC induced the formation and release of HSP70-containing and IL-1β-containing exosomes via an ASMase-dependent mechanism. Taken together, the results suggest that oxLDL and oxLDL-IC differentially regulate ASMase activity, and the pro-inflammatory responses to oxLDL-IC are mediated by prolonged activation of ASMase. These findings may contribute to increased understanding of mechanisms mediating macrophage involvement in atherosclerosis.

Indexed as

PhagocytosisAnimalsCell LineCytokinesExosomesHumansLipoproteins, LDLLysosomesMacrophagesMiceSphingomyelin PhosphodiesteraseCytokinesLipoproteins, LDLoxidized low density lipoproteinSphingomyelin Phosphodiesterase

Identifiers

PMID22236141
PMCPMC3372755
OpenAlexW1589760452

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.