AUTHOR=Shu Fei , Chen Jiahuan , Ma Xiaojie , Fan Yunzhou , Yu Li , Zheng Wencheng , Amrein Matthias W. , Xia Tie , Shi Yan TITLE=Cholesterol Crystal-Mediated Inflammation Is Driven by Plasma Membrane Destabilization JOURNAL=Frontiers in Immunology VOLUME=9 YEAR=2018 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01163 DOI=10.3389/fimmu.2018.01163 ISSN=1664-3224 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.