Evidence map›Paper›PMID 19812252›Full record

ArticleMolecular biology of the cell2009

Macrophages create an acidic extracellular hydrolytic compartment to digest aggregated lipoproteins.

Abigail S Haka, Inna Grosheva, Ethan Chiang, Adina R Buxbaum, Barbara A Baird, Lynda M Pierini, Frederick R Maxfield

Abstract read
In one paragraph

Article in Molecular biology of the cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
–field-weighted citation impact
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

72 citing papers in PubMed.

  1. Review
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  13. Review
  14. The Functions of SARS-CoV-2 Receptors in Diabetes-Related Severe COVID-19.International journal of molecular sciences · 2024
    Review
  15. Article
  16. Recent insights into lysosomal acid lipase deficiency.Trends in molecular medicine · 2023
    Review
  17. Review
  18. Review
  19. Article
  20. Review

12 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

7 authors.

Abigail S HakaDepartment of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA.
Inna Grosheva
Ethan Chiang
Adina R Buxbaum
Barbara A Baird
Lynda M Pierini
Frederick R Maxfield

Funding

Sculpting the atherosclerotic plaque by neurotrophinsP01HL072942 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI HAJJAR, DAVID P · 2003 to 2007
$10.3M
Macrophage-Lipoprotein InteractionsR01HL093324 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI MAXFIELD, FREDERICK R. · 2009 to 2025
$6.7M
RECEPTOR-MEDIATED ENDOCYTOSIS: MECHANISM AND FUNCTIONR37DK027083 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI MAXFIELD, FREDERICK R. · 1993 to 2014
$6.5M
STUCTURE-FUNCTION RELATIONSHIPS OF IMMUNORECEPTORSR01AI018306 · NIAID · CORNELL UNIVERSITY ITHACA · PI BAIRD, BARBARA A · 1985 to 2014
$5.3M
INTERACTION OF ATHEROGENIC LIPOPROTEINS WITH MACROPHAGESR01HL057560 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI TABAS, IRA A · 1997 to 2010
$4.3M
NHLBI NIH HHS P01 HL072942NHLBI NIH HHS P01-HL072942NHLBI NIH HHS R01 HL057560NHLBI NIH HHS R01 HL093324NIAID NIH HHS R01 AI018306NIDDK NIH HHS R37 DK027083NIDDK NIH HHS R37-DK27083
6 · The paper itself

Abstract

A critical event in atherogenesis is the interaction of macrophages with subendothelial lipoproteins. Although most studies model this interaction by incubating macrophages with monomeric lipoproteins, macrophages in vivo encounter lipoproteins that are aggregated. The physical features of the lipoproteins require distinctive mechanisms for their uptake. We show that macrophages create an extracellular, acidic, hydrolytic compartment to carry out digestion of aggregated low-density lipoproteins. We demonstrate delivery of lysosomal contents to these specialized compartments and their acidification by vacuolar ATPase, enabling aggregate catabolism by lysosomal acid hydrolases. We observe transient sealing of portions of the compartments, allowing formation of an "extracellular" proton gradient. An increase in free cholesterol is observed in aggregates contained in these compartments. Thus, cholesteryl ester hydrolysis can occur extracellularly in a specialized compartment, a lysosomal synapse, during the interaction of macrophages with aggregated low-density lipoprotein. A detailed understanding of these processes is essential for developing strategies to prevent atherosclerosis.

Indexed as

AnimalsAtherosclerosisCell LineCell MembraneCholesterolCholesterol EstersExocytosisFoam CellsHumansHydrogen-Ion ConcentrationHydrolysisLipoproteins, LDLLysosomesMacrophagesMicePermeabilityCholesterolCholesterol EstersLipoproteins, LDL

Identifiers

PMID19812252
PMCPMC2785736

What OpenQuestion holds

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Registered trials

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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.