Receptor-mediated and bulk-phase endocytosis cause macrophage and cholesterol accumulation in Niemann-Pick C disease
These studies explored the roles of receptor-mediated and bulk-phase endocytosis as well as macrophage infiltration in the accumulation of cholesterol in the mouse with Niemann-Pick type C (NPC) disease. Uptake of LDL-cholesterol varied from 514 μg/day in the liver to zero in the central nervous sys...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2007-08-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520425076 |
| _version_ | 1818920496448667648 |
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| author | Benny Liu Chonglun Xie James A. Richardson Stephen D. Turley John M. Dietschy |
| author_facet | Benny Liu Chonglun Xie James A. Richardson Stephen D. Turley John M. Dietschy |
| author_sort | Benny Liu |
| collection | DOAJ |
| description | These studies explored the roles of receptor-mediated and bulk-phase endocytosis as well as macrophage infiltration in the accumulation of cholesterol in the mouse with Niemann-Pick type C (NPC) disease. Uptake of LDL-cholesterol varied from 514 μg/day in the liver to zero in the central nervous system. In animals lacking LDL receptors, liver uptake remained about the same (411 μg/day), but more cholesterol was taken up in extrahepatic organs. This uptake was unaffected by the reductive methylation of LDL and consistent with bulk-phase endocytosis. All tissues accumulated cholesterol in mice lacking NPC1 function, but this accumulation was decreased in adrenal, unchanged in liver, and increased in organs like spleen and lung when LDL receptor function was also deleted. Over 56 days, the spleen and lung accumulated amounts of cholesterol greater than predicted, and these organs were heavily infiltrated with macrophages. This accumulation of both cholesterol and macrophages was increased by deleting LDL receptor function. These observations indicate that both receptor-mediated and bulk-phase endocytosis of lipoproteins, as well as macrophage infiltration, contribute to the cholesterol accumulation seen in NPC disease. These macrophages may also play a role in parenchymal cell death in this syndrome. |
| first_indexed | 2024-12-20T01:22:41Z |
| format | Article |
| id | doaj.art-c6eab312baec43eca4502d1c6e112cc3 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-20T01:22:41Z |
| publishDate | 2007-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-c6eab312baec43eca4502d1c6e112cc32022-12-21T19:58:23ZengElsevierJournal of Lipid Research0022-22752007-08-0148817101723Receptor-mediated and bulk-phase endocytosis cause macrophage and cholesterol accumulation in Niemann-Pick C diseaseBenny Liu0Chonglun Xie1James A. Richardson2Stephen D. Turley3John M. Dietschy4Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, TX 75390-9151Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, TX 75390-9151Department of Pathology, University of Texas Southwestern Medical School, Dallas, TX 75390-9151Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, TX 75390-9151Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, TX 75390-9151These studies explored the roles of receptor-mediated and bulk-phase endocytosis as well as macrophage infiltration in the accumulation of cholesterol in the mouse with Niemann-Pick type C (NPC) disease. Uptake of LDL-cholesterol varied from 514 μg/day in the liver to zero in the central nervous system. In animals lacking LDL receptors, liver uptake remained about the same (411 μg/day), but more cholesterol was taken up in extrahepatic organs. This uptake was unaffected by the reductive methylation of LDL and consistent with bulk-phase endocytosis. All tissues accumulated cholesterol in mice lacking NPC1 function, but this accumulation was decreased in adrenal, unchanged in liver, and increased in organs like spleen and lung when LDL receptor function was also deleted. Over 56 days, the spleen and lung accumulated amounts of cholesterol greater than predicted, and these organs were heavily infiltrated with macrophages. This accumulation of both cholesterol and macrophages was increased by deleting LDL receptor function. These observations indicate that both receptor-mediated and bulk-phase endocytosis of lipoproteins, as well as macrophage infiltration, contribute to the cholesterol accumulation seen in NPC disease. These macrophages may also play a role in parenchymal cell death in this syndrome.http://www.sciencedirect.com/science/article/pii/S0022227520425076hepatic dysfunctionlung failurelow density lipoprotein receptorlysosomal cholesterolapoptosisneurodegeneration |
| spellingShingle | Benny Liu Chonglun Xie James A. Richardson Stephen D. Turley John M. Dietschy Receptor-mediated and bulk-phase endocytosis cause macrophage and cholesterol accumulation in Niemann-Pick C disease Journal of Lipid Research hepatic dysfunction lung failure low density lipoprotein receptor lysosomal cholesterol apoptosis neurodegeneration |
| title | Receptor-mediated and bulk-phase endocytosis cause macrophage and cholesterol accumulation in Niemann-Pick C disease |
| title_full | Receptor-mediated and bulk-phase endocytosis cause macrophage and cholesterol accumulation in Niemann-Pick C disease |
| title_fullStr | Receptor-mediated and bulk-phase endocytosis cause macrophage and cholesterol accumulation in Niemann-Pick C disease |
| title_full_unstemmed | Receptor-mediated and bulk-phase endocytosis cause macrophage and cholesterol accumulation in Niemann-Pick C disease |
| title_short | Receptor-mediated and bulk-phase endocytosis cause macrophage and cholesterol accumulation in Niemann-Pick C disease |
| title_sort | receptor mediated and bulk phase endocytosis cause macrophage and cholesterol accumulation in niemann pick c disease |
| topic | hepatic dysfunction lung failure low density lipoprotein receptor lysosomal cholesterol apoptosis neurodegeneration |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520425076 |
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