دورية أكاديمية
Monocyte-Derived Dendritic Cells Upregulate Extracellular Catabolism of Aggregated Low-Density Lipoprotein on Maturation, Leading to Foam Cell Formation.
| العنوان: | Monocyte-Derived Dendritic Cells Upregulate Extracellular Catabolism of Aggregated Low-Density Lipoprotein on Maturation, Leading to Foam Cell Formation. |
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| المؤلفون: | Haka AS; 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.)., Singh RK; 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.)., Grosheva I; 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.)., Hoffner H; 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.)., Capetillo-Zarate E; 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.)., Chin HF; 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.)., Anandasabapathy N; 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.)., Maxfield FR; 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. |
| المصدر: | Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2015 Oct; Vol. 35 (10), pp. 2092-103. Date of Electronic Publication: 2015 Aug 20. |
| نوع المنشور: | Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 9505803 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4636 (Electronic) Linking ISSN: 10795642 NLM ISO Abbreviation: Arterioscler Thromb Vasc Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1998- : Baltimore, Md. : Lippincott Williams & Wilkins Original Publication: Dallas, TX : American Heart Association, c1995- |
| مواضيع طبية MeSH: | Atherosclerosis/*genetics , Atherosclerosis/*pathology , Dendritic Cells/*cytology , Foam Cells/*cytology , Lipoproteins, LDL/*metabolism , Phagocytosis/*physiology, Animals ; Cells, Cultured ; Dendritic Cells/metabolism ; Disease Models, Animal ; Foam Cells/metabolism ; Humans ; Mice ; Mice, Knockout ; Monocytes/cytology ; Monocytes/metabolism ; Phagocytosis/genetics ; Random Allocation ; Transcriptional Activation ; Up-Regulation |
| مستخلص: | 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). Approach and 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. (© 2015 American Heart Association, Inc.) |
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| معلومات مُعتمدة: | R01-HL092234 United States HL NHLBI NIH HHS; R01 HL093324 United States HL NHLBI NIH HHS; R00 HL092234 United States HL NHLBI NIH HHS; R37-DK27083 United States DK NIDDK NIH HHS; R37 DK027083 United States DK NIDDK NIH HHS; K99 HL092234 United States HL NHLBI NIH HHS |
| فهرسة مساهمة: | Keywords: LDL; atherosclerosis; dendritic cells; foam cells; lipoproteins; phagocytosis |
| المشرفين على المادة: | 0 (Lipoproteins, LDL) |
| تواريخ الأحداث: | Date Created: 20150822 Date Completed: 20151217 Latest Revision: 20181113 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC4583358 |
| DOI: | 10.1161/ATVBAHA.115.305843 |
| PMID: | 26293468 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1524-4636 |
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| DOI: | 10.1161/ATVBAHA.115.305843 |