2. Academic Validation
  3. Release of cholesterol-rich particles from the macrophage plasma membrane during movement of filopodia and lamellipodia

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

  • Elife. 2019 Sep 5;8:e50231. doi: 10.7554/eLife.50231.
Xuchen Hu 1,  Thomas A Weston 1,  Cuiwen He 1,  Rachel S Jung 1,  Patrick J Heizer 1,  Brian D Young 2,  Yiping Tu 1,  Peter Tontonoz 3,  James A Wohlschlegel 2,  Haibo Jiang 1 4,  Stephen G Young 1 5,  Loren G Fong 1
Affiliations

Affiliations

  • 1 Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States.
  • 2 Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, United States.
  • 3 Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, United States.
  • 4 School of Molecular Sciences, University of Western Australia, Perth, Australia.
  • 5 Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States.
PMID: 31486771 DOI: 10.7554/eLife.50231
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.

Keywords

NanoSIMS; accessible cholesterol; biochemistry; cell biology; chemical biology; cholesterol efflux; focal adhesions; mouse.

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