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Front Immunol. 2018 May 29;9:1163. doi: 10.3389/fimmu.2018.01163. eCollection 2018.

Cholesterol Crystal-Mediated Inflammation Is Driven by Plasma Membrane Destabilization.

Author information

1
Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, School of Life Sciences, Peking University, Beijing, China.
2
Department of Basic Medical Sciences, Center for Life Sciences, Institute for Immunology, Beijing Key Lab for Immunological Research on Chronic Diseases, Tsinghua University, Beijing, China.
3
Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, China.
4
Department of Cell Biology, Snyder Institute, University of Calgary, Calgary, AB, Canada.
5
Department of Anatomy, Snyder Institute, University of Calgary, Calgary, AB, Canada.
6
Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute, University of Calgary, Calgary, AB, Canada.

Abstract

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.

KEYWORDS:

cell death; cholesterol crystals; inflammation; membrane rupture; signal free

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