T cell exosomes induce cholesterol accumulation in human monocytes via phosphatidylserine receptor.
Activated T lymphocytes release vesicles, termed exosomes, enriched in cholesterol and exposing phosphatidylserine (PS) at their outer membrane leaflet. Although CD4(+) activated T lymphocytes infiltrate an atherosclerotic plaque, the effects of T cell exosomes on the atheroma-associated cells are not known. We report here that exosomes isolated from the supernatants of activated human CD4(+) T cells enhance cholesterol accumulation in cultured human monocytes and THP-1 cells. Lipid droplets found in the cytosol of exosome-treated monocytes contained both cholesterol ester and free cholesterol. Anti-phosphatidylserine receptor antibodies recognized surface protein on the monocyte plasma membrane and prevented exosome-induced cholesterol accumulation, indicating that exosome internalization is mediated via endogenous phosphatidylserine receptor. The production of proinflammatory cytokine TNF-alpha enhanced in parallel with monocyte cholesterol accumulation. Our data strongly indicate that exosomes released by activated T cells may represent a powerful, previously unknown, atherogenic factor.
Zakharova
Liudmila
L
Department of Physiology and Membrane Biology, University of California Davis, Davis, California 95616, USA.
Svetlova
Maria
M
Fomina
Alla F
AF
D000328:Adult; D000906:Antibodies; D050197:Atherosclerosis / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000906:Antibodies; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; C408123:phosphatidylserine receptor; D002784:Cholesterol