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

Xuchen Hu, Thomas A. Weston, Cuiwen He, Rachel S. Jung, Patrick J. Heizer, Brian D. Young, Yiping Tu, Peter Tontonoz, James A. Wohlschlegel, Haibo Jiang, Stephen G. Young, Loren G. Fong

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournaleLife
Volume8
DOIs
Publication statusPublished - 5 Sep 2019

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Pseudopodia
Macrophages
Cell membranes
Cholesterol
Cell Membrane
Myosin Type II
Perforin
Sphingolipids
Focal Adhesions
Confocal microscopy
Peritoneal Macrophages
Atherosclerotic Plaques
Locomotion
Confocal Microscopy
Cell Movement
Actins
Adhesion
Cells
Imaging techniques
Substrates

Cite this

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. In: eLife. 2019 ; Vol. 8.
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abstract = "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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author = "Xuchen Hu and Weston, {Thomas A.} and Cuiwen He and Jung, {Rachel S.} and Heizer, {Patrick J.} and Young, {Brian D.} and Yiping Tu and Peter Tontonoz and Wohlschlegel, {James A.} and Haibo Jiang and Young, {Stephen G.} and Fong, {Loren G.}",
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Hu, X, Weston, TA, He, C, Jung, RS, Heizer, PJ, Young, BD, Tu, Y, Tontonoz, P, Wohlschlegel, JA, Jiang, H, Young, SG & Fong, LG 2019, 'Release of cholesterol-rich particles from the macrophage plasma membrane during movement of filopodia and lamellipodia' eLife, vol. 8. https://doi.org/10.7554/eLife.50231

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.

In: eLife, Vol. 8, 05.09.2019.

Research output: Contribution to journalArticle

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AU - Hu, Xuchen

AU - Weston, Thomas A.

AU - He, Cuiwen

AU - Jung, Rachel S.

AU - Heizer, Patrick J.

AU - Young, Brian D.

AU - Tu, Yiping

AU - Tontonoz, Peter

AU - Wohlschlegel, James A.

AU - Jiang, Haibo

AU - Young, Stephen G.

AU - Fong, Loren G.

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AB - 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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