Release of cholesterol-rich particles from the macrophage plasma membrane during movement of filopodia and lamellipodia.
NanoSIMS
accessible cholesterol
biochemistry
cell biology
chemical biology
cholesterol efflux
focal adhesions
mouse
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
05 09 2019
05 09 2019
Historique:
received:
16
07
2019
accepted:
04
09
2019
pubmed:
6
9
2019
medline:
7
2
2020
entrez:
6
9
2019
Statut:
epublish
Résumé
Cultured mouse peritoneal macrophages release large numbers of ~30-nm cholesterol-rich particles. Here, we show that those particles represent fragments of the plasma membrane that are pulled away and left behind during the projection and retraction of filopodia and lamellipodia. Consistent with this finding, the particles are enriched in proteins found in focal adhesions, which attach macrophages to the substrate. The release of particles is abolished by blocking cell movement (either by depolymerizing actin with latrunculin A or by inhibiting myosin II with blebbistatin). Confocal microscopy and NanoSIMS imaging studies revealed that the plasma membrane-derived particles are enriched in 'accessible cholesterol' (a mobile pool of cholesterol detectable with the modified cytolysin ALO-D4) but not in sphingolipid-sequestered cholesterol [a pool detectable with ostreolysin A (OlyA)]. The discovery that macrophages release cholesterol-rich particles during cellular locomotion is likely relevant to cholesterol efflux and could contribute to extracellular cholesterol deposition in atherosclerotic plaques.
Identifiants
pubmed: 31486771
doi: 10.7554/eLife.50231
pii: 50231
pmc: PMC6750930
doi:
pii:
Substances chimiques
Proteins
0
Cholesterol
97C5T2UQ7J
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : HL125335
Pays : United States
Organisme : Fondation Leducq
ID : 12CVD04
Pays : International
Organisme : NHLBI NIH HHS
ID : HL090553
Pays : United States
Organisme : Ruth L Kirschstein National Research Service Award
ID : T32HL69766
Pays : International
Organisme : NHLBI NIH HHS
ID : HL087228
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL146358
Pays : United States
Organisme : Australian Research Council
ID : Discovery Early Career Researcher
Pays : International
Organisme : Fondation Leducq
ID : 12CVD04).
Pays : International
Organisme : Cancer Council Western Australia
ID : Early Career Investigator Grant
Pays : International
Organisme : NHLBI NIH HHS
ID : HL125335)
Pays : United States
Organisme : Ruth L Kirschstein National Research Service Award
ID : T32HL69766)
Pays : International
Informations de copyright
© 2019, Hu et al.
Déclaration de conflit d'intérêts
XH, TW, CH, RJ, PH, BY, YT, JW, HJ, SY, LF No competing interests declared, PT Reviewing editor, eLife
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