title: Monocyte-Derived Dendritic Cells Upregulate Extracellular Catabolism of Aggregated Low-Density Lipoprotein on Maturation, Leading to Foam Cell Formation.
abstract: OBJECTIVE
  Although dendritic cells are known to play a role in atherosclerosis, few studies have examined the contribution of the wide variety of dendritic cell subsets. Accordingly, their roles in atherogenesis remain largely unknown. We investigated the ability of different dendritic cell subsets to become foam cells after contact with aggregated low-density lipoprotein (LDL; the predominant form of LDL found in atherosclerotic plaques).
  
  
  RESULTS
  We demonstrate that both murine and human monocyte-derived dendritic cells use exophagy to degrade aggregated LDL, leading to foam cell formation, whereas monocyte-independent dendritic cells are unable to clear LDL aggregates by this mechanism. Exophagy is a catabolic process in which objects that cannot be internalized by phagocytosis (because of their size or association with extracellular structures) are initially digested in an extracellular acidic lytic compartment. Surprisingly, we found that monocyte-derived dendritic cells upregulate exophagy on maturation. This contrasts various forms of endocytic internalization in dendritic cells, which decrease on maturation. Finally, we show that our in vitro results are consistent with dendritic cell lipid accumulation in plaques of an ApoE(-/-) mouse model of atherosclerosis.
  
  
  CONCLUSIONS
  Our results show that monocyte-derived dendritic cells use exophagy to degrade aggregated LDL and become foam cells, whereas monocyte-independent dendritic cells are unable to clear LDL deposits. Furthermore, we find that exophagy is upregulated on dendritic cell maturation. Thus, exophagy-mediated foam cell formation in monocyte-derived dendritic cells could play a significant role in atherogenesis.
authors: From the Department of Biochemistry, Weill Cornell Medical College, New York, NY (A.S.H., R.K.S., I.G., H.H., E.C.-Z., H.F.C., F.R.M.); and Department of Dermatology, Harvard Skin Disease Research Center, Bringham and Women's Hospital, Boston, MA (N.A.).
authors: Abigail S
authors: AS
authors: Haka
authors: From the Department of Biochemistry, Weill Cornell Medical College, New York, NY (A.S.H., R.K.S., I.G., H.H., E.C.-Z., H.F.C., F.R.M.); and Department of Dermatology, Harvard Skin Disease Research Center, Bringham and Women's Hospital, Boston, MA (N.A.).
authors: Rajesh K
authors: RK
authors: Singh
authors: From the Department of Biochemistry, Weill Cornell Medical College, New York, NY (A.S.H., R.K.S., I.G., H.H., E.C.-Z., H.F.C., F.R.M.); and Department of Dermatology, Harvard Skin Disease Research Center, Bringham and Women's Hospital, Boston, MA (N.A.).
authors: Inna
authors: I
authors: Grosheva
authors: From the Department of Biochemistry, Weill Cornell Medical College, New York, NY (A.S.H., R.K.S., I.G., H.H., E.C.-Z., H.F.C., F.R.M.); and Department of Dermatology, Harvard Skin Disease Research Center, Bringham and Women's Hospital, Boston, MA (N.A.).
authors: Haley
authors: H
authors: Hoffner
authors: From the Department of Biochemistry, Weill Cornell Medical College, New York, NY (A.S.H., R.K.S., I.G., H.H., E.C.-Z., H.F.C., F.R.M.); and Department of Dermatology, Harvard Skin Disease Research Center, Bringham and Women's Hospital, Boston, MA (N.A.).
authors: Estibaliz
authors: E
authors: Capetillo-Zarate
authors: From the Department of Biochemistry, Weill Cornell Medical College, New York, NY (A.S.H., R.K.S., I.G., H.H., E.C.-Z., H.F.C., F.R.M.); and Department of Dermatology, Harvard Skin Disease Research Center, Bringham and Women's Hospital, Boston, MA (N.A.).
authors: Harvey F
authors: HF
authors: Chin
authors: From the Department of Biochemistry, Weill Cornell Medical College, New York, NY (A.S.H., R.K.S., I.G., H.H., E.C.-Z., H.F.C., F.R.M.); and Department of Dermatology, Harvard Skin Disease Research Center, Bringham and Women's Hospital, Boston, MA (N.A.).
authors: Niroshana
authors: N
authors: Anandasabapathy
authors: From the Department of Biochemistry, Weill Cornell Medical College, New York, NY (A.S.H., R.K.S., I.G., H.H., E.C.-Z., H.F.C., F.R.M.); and Department of Dermatology, Harvard Skin Disease Research Center, Bringham and Women's Hospital, Boston, MA (N.A.). frmaxfie@med.cornell.edu.
authors: Frederick R
authors: FR
authors: Maxfield
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics* / Q000473:pathology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D004195:Disease Models, Animal; D005487:Foam Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D010587:Phagocytosis / Q000235:genetics / Q000502:physiology*; D011897:Random Allocation; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D008077:Lipoproteins, LDL
keywords: LDL; atherosclerosis; dendritic cells; foam cells; lipoproteins; phagocytosis