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Release of cholesterol-rich particles from the macrophage plasma membrane during movement of filopodia and lamellipodia

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 thi...

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Autores principales: Hu, Xuchen, Weston, Thomas A, He, Cuiwen, Jung, Rachel S, Heizer, Patrick J, Young, Brian D, Tu, Yiping, Tontonoz, Peter, Wohlschlegel, James A, Jiang, Haibo, Young, Stephen G, Fong, Loren G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750930/
https://www.ncbi.nlm.nih.gov/pubmed/31486771
http://dx.doi.org/10.7554/eLife.50231
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author Hu, Xuchen
Weston, Thomas A
He, Cuiwen
Jung, Rachel S
Heizer, Patrick J
Young, Brian D
Tu, Yiping
Tontonoz, Peter
Wohlschlegel, James A
Jiang, Haibo
Young, Stephen G
Fong, Loren G
author_facet Hu, Xuchen
Weston, Thomas A
He, Cuiwen
Jung, Rachel S
Heizer, Patrick J
Young, Brian D
Tu, Yiping
Tontonoz, Peter
Wohlschlegel, James A
Jiang, Haibo
Young, Stephen G
Fong, Loren G
author_sort Hu, Xuchen
collection PubMed
description 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.
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spelling pubmed-67509302019-09-20 Release of cholesterol-rich particles from the macrophage plasma membrane during movement of filopodia and lamellipodia Hu, Xuchen Weston, Thomas A He, Cuiwen Jung, Rachel S Heizer, Patrick J Young, Brian D Tu, Yiping Tontonoz, Peter Wohlschlegel, James A Jiang, Haibo Young, Stephen G Fong, Loren G eLife Biochemistry and Chemical Biology 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. eLife Sciences Publications, Ltd 2019-09-05 /pmc/articles/PMC6750930/ /pubmed/31486771 http://dx.doi.org/10.7554/eLife.50231 Text en © 2019, Hu et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biochemistry and Chemical Biology
Hu, Xuchen
Weston, Thomas A
He, Cuiwen
Jung, Rachel S
Heizer, Patrick J
Young, Brian D
Tu, Yiping
Tontonoz, Peter
Wohlschlegel, James A
Jiang, Haibo
Young, Stephen G
Fong, Loren G
Release of cholesterol-rich particles from the macrophage plasma membrane during movement of filopodia and lamellipodia
title Release of cholesterol-rich particles from the macrophage plasma membrane during movement of filopodia and lamellipodia
title_full Release of cholesterol-rich particles from the macrophage plasma membrane during movement of filopodia and lamellipodia
title_fullStr Release of cholesterol-rich particles from the macrophage plasma membrane during movement of filopodia and lamellipodia
title_full_unstemmed Release of cholesterol-rich particles from the macrophage plasma membrane during movement of filopodia and lamellipodia
title_short Release of cholesterol-rich particles from the macrophage plasma membrane during movement of filopodia and lamellipodia
title_sort release of cholesterol-rich particles from the macrophage plasma membrane during movement of filopodia and lamellipodia
topic Biochemistry and Chemical Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750930/
https://www.ncbi.nlm.nih.gov/pubmed/31486771
http://dx.doi.org/10.7554/eLife.50231
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