Cholesterol Crystal-Mediated Inflammation Is Driven by Plasma Membrane Destabilization
Atherosclerosis is driven by an inflammatory milieu in the walls of artery vessels. Initiated early in life, it progresses to plaque formation and form cell accumulation. A culprit in this cascade is the deposition of cholesterol crystals (CC). The involvement of smaller crystals in the early stage...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-05-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.01163/full |
| _version_ | 1828388516157980672 |
|---|---|
| author | Fei Shu Fei Shu Jiahuan Chen Xiaojie Ma Yunzhou Fan Li Yu Wencheng Zheng Matthias W. Amrein Matthias W. Amrein Tie Xia Yan Shi Yan Shi |
| author_facet | Fei Shu Fei Shu Jiahuan Chen Xiaojie Ma Yunzhou Fan Li Yu Wencheng Zheng Matthias W. Amrein Matthias W. Amrein Tie Xia Yan Shi Yan Shi |
| author_sort | Fei Shu |
| collection | DOAJ |
| description | Atherosclerosis is driven by an inflammatory milieu in the walls of artery vessels. Initiated early in life, it progresses to plaque formation and form cell accumulation. A culprit in this cascade is the deposition of cholesterol crystals (CC). The involvement of smaller crystals in the early stage of atherosclerotic changes may be critical to the long-term pathological development. How these small crystals initiate the pro-inflammatory events is under study. We report here an unexpected mechanism that microscopic CC interact with cellular membrane in a phagocytosis-independent manner. The binding of these crystals extracts cholesterol from the cell surface. This process causes a sudden catastrophic rupture of plasma membrane and necrosis of the bound cells independent of any known cell death-inducing pathways, releasing inflammatory agents associated with the necrotic cell death. Our results, therefore, reveal a biophysical aspect of CC in potentially mediating the inflammatory progress in atherosclerosis. |
| first_indexed | 2024-12-10T06:14:41Z |
| format | Article |
| id | doaj.art-3b953e838f8f4e7c97b75fec1ea9c6af |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T06:14:41Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3b953e838f8f4e7c97b75fec1ea9c6af2022-12-22T01:59:29ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-05-01910.3389/fimmu.2018.01163360430Cholesterol Crystal-Mediated Inflammation Is Driven by Plasma Membrane DestabilizationFei Shu0Fei Shu1Jiahuan Chen2Xiaojie Ma3Yunzhou Fan4Li Yu5Wencheng Zheng6Matthias W. Amrein7Matthias W. Amrein8Tie Xia9Yan Shi10Yan Shi11Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, School of Life Sciences, Peking University, Beijing, ChinaDepartment of Basic Medical Sciences, Center for Life Sciences, Institute for Immunology, Beijing Key Lab for Immunological Research on Chronic Diseases, Tsinghua University, Beijing, ChinaDepartment of Basic Medical Sciences, Center for Life Sciences, Institute for Immunology, Beijing Key Lab for Immunological Research on Chronic Diseases, Tsinghua University, Beijing, ChinaDepartment of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaDepartment of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaDepartment of Basic Medical Sciences, Center for Life Sciences, Institute for Immunology, Beijing Key Lab for Immunological Research on Chronic Diseases, Tsinghua University, Beijing, ChinaDepartment of Basic Medical Sciences, Center for Life Sciences, Institute for Immunology, Beijing Key Lab for Immunological Research on Chronic Diseases, Tsinghua University, Beijing, ChinaDepartment of Cell Biology, Snyder Institute, University of Calgary, Calgary, AB, CanadaDepartment of Anatomy, Snyder Institute, University of Calgary, Calgary, AB, CanadaDepartment of Basic Medical Sciences, Center for Life Sciences, Institute for Immunology, Beijing Key Lab for Immunological Research on Chronic Diseases, Tsinghua University, Beijing, ChinaDepartment of Basic Medical Sciences, Center for Life Sciences, Institute for Immunology, Beijing Key Lab for Immunological Research on Chronic Diseases, Tsinghua University, Beijing, ChinaDepartment of Microbiology, Immunology and Infectious Diseases, Snyder Institute, University of Calgary, Calgary, AB, CanadaAtherosclerosis is driven by an inflammatory milieu in the walls of artery vessels. Initiated early in life, it progresses to plaque formation and form cell accumulation. A culprit in this cascade is the deposition of cholesterol crystals (CC). The involvement of smaller crystals in the early stage of atherosclerotic changes may be critical to the long-term pathological development. How these small crystals initiate the pro-inflammatory events is under study. We report here an unexpected mechanism that microscopic CC interact with cellular membrane in a phagocytosis-independent manner. The binding of these crystals extracts cholesterol from the cell surface. This process causes a sudden catastrophic rupture of plasma membrane and necrosis of the bound cells independent of any known cell death-inducing pathways, releasing inflammatory agents associated with the necrotic cell death. Our results, therefore, reveal a biophysical aspect of CC in potentially mediating the inflammatory progress in atherosclerosis.https://www.frontiersin.org/article/10.3389/fimmu.2018.01163/fullcholesterol crystalscell deathinflammationmembrane rupturesignal free |
| spellingShingle | Fei Shu Fei Shu Jiahuan Chen Xiaojie Ma Yunzhou Fan Li Yu Wencheng Zheng Matthias W. Amrein Matthias W. Amrein Tie Xia Yan Shi Yan Shi Cholesterol Crystal-Mediated Inflammation Is Driven by Plasma Membrane Destabilization Frontiers in Immunology cholesterol crystals cell death inflammation membrane rupture signal free |
| title | Cholesterol Crystal-Mediated Inflammation Is Driven by Plasma Membrane Destabilization |
| title_full | Cholesterol Crystal-Mediated Inflammation Is Driven by Plasma Membrane Destabilization |
| title_fullStr | Cholesterol Crystal-Mediated Inflammation Is Driven by Plasma Membrane Destabilization |
| title_full_unstemmed | Cholesterol Crystal-Mediated Inflammation Is Driven by Plasma Membrane Destabilization |
| title_short | Cholesterol Crystal-Mediated Inflammation Is Driven by Plasma Membrane Destabilization |
| title_sort | cholesterol crystal mediated inflammation is driven by plasma membrane destabilization |
| topic | cholesterol crystals cell death inflammation membrane rupture signal free |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.01163/full |
| work_keys_str_mv | AT feishu cholesterolcrystalmediatedinflammationisdrivenbyplasmamembranedestabilization AT feishu cholesterolcrystalmediatedinflammationisdrivenbyplasmamembranedestabilization AT jiahuanchen cholesterolcrystalmediatedinflammationisdrivenbyplasmamembranedestabilization AT xiaojiema cholesterolcrystalmediatedinflammationisdrivenbyplasmamembranedestabilization AT yunzhoufan cholesterolcrystalmediatedinflammationisdrivenbyplasmamembranedestabilization AT liyu cholesterolcrystalmediatedinflammationisdrivenbyplasmamembranedestabilization AT wenchengzheng cholesterolcrystalmediatedinflammationisdrivenbyplasmamembranedestabilization AT matthiaswamrein cholesterolcrystalmediatedinflammationisdrivenbyplasmamembranedestabilization AT matthiaswamrein cholesterolcrystalmediatedinflammationisdrivenbyplasmamembranedestabilization AT tiexia cholesterolcrystalmediatedinflammationisdrivenbyplasmamembranedestabilization AT yanshi cholesterolcrystalmediatedinflammationisdrivenbyplasmamembranedestabilization AT yanshi cholesterolcrystalmediatedinflammationisdrivenbyplasmamembranedestabilization |