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This article is available online at http://www.jlr.org it can be mobilized from these cells by components of the HDL system. In this process, either preformed plasmaderived HDL or HDL generated by cells such as macrophages within atherosclerotic plaques, function as acceptors of excess cellular cholesterol. Excess cellular cholesterol is believed to be transferred to HDL from either intracellular or plasma membrane pools of cholesterol.ABCA1 and ABCG1 both function in mediating cellular cholesterol effl ux and contributing to reverse cholesterol transport ( 3-5 ). ABCA1 mediates phospholipidation of ApoA-I, which then functions as an HDL cholesterol acceptor, stimulating cholesterol effl ux. In contrast, ABCG1 mediates cellular cholesterol effl ux to preformed HDL. HDL binds poorly to ABCA1 and ABCG1; nevertheless, both proteins mediate transfer of cholesterol from cells to HDL ( 6-10 ). While ABCA1 can mediate cholesterol effl ux by generating nascent HDL from the simultaneous effl ux of phospholipid and cholesterol, ABCA1 can also effl ux cholesterol to preformed mature HDL ( 11 ). The possible molecular mechanisms for these cholesterol transfers have been recently reviewed ( 4 ). Hypothetical cholesterol microdomains are featured in some of the models of cellular cholesterol effl ux.Besides cellular cholesterol effl ux to HDL, under certain conditions, cells release cholesterol in the form of spherical microparticles. Microparticles containing cholesterol and phospholipid are released into culture medium by cAMP-treated J774 mouse macrophages ( 12, 13 ), cholesterol-enriched human monocyte-derived macrophages ( 14 ), and BHK cells following increased expression of ABCA1 ( 12 ). All these microparticles lack HDL-associated apolipoproteins and do not appear to be precursors to HDL.Previously, we described an extracellular matrix-associated pool of cholesterol that functions in delivering cholesterol Abstract We previously reported that cholesterol-enriched macrophages excrete cholesterol into the extracellular matrix. A monoclonal antibody that detects cholesterol microdomains labels the deposited extracellular particles. Macrophage deposition of extracellular cholesterol depends, in part, on ABCG1, and this cholesterol can be mobilized by HDL components of the reverse cholesterol transport process. The objective of the current study was to determine whether ABCA1 also contributes to macrophage deposition of extracellular cholesterol. ABCA1 functioned in extracellular cholesterol deposition. The liver X receptor agonist, TO901317 (TO9), an ABCA1-inducing factor, restored cholesterol deposition that was absent in cholesterol-enriched ABCG1 ؊ / ؊ mouse macrophages. In addition, the ABCA1 inhibitor, probucol, blocked the increment in cholesterol deposited by TO9-treated wild-type macrophages, and completely inhibited deposition from TO9-treated ABCG1 ؊ / ؊ macrophages. Lastly, ABCA1؊ / ؊ macrophages deposited much less extracellular cholesterol than wild-type macrophages. These fi ndings demonstrate a novel functi...

The ongoing COVID-19 global pandemic has necessitated evaluating various disinfection technologies for reducing viral transmission in public settings. Ultraviolet (UV) radiation can inactivate pathogens and viruses but more insight is needed into the performance of different UV wavelengths and their applications. We observed greater than a 3-log reduction of SARS-CoV-2 infectivity with a dose of 12.5 mJ/cm2 of 254 nm UV light when the viruses were suspended in PBS, while a dose of 25 mJ/cm2 was necessary to achieve a similar reduction when they were in an EMEM culture medium containing 2%(v/v) FBS, highlighting the critical effect of media in which the virus is suspended, given that SARS-CoV-2 is always aerosolized when airborne or deposited on a surface. It was found that SARS-CoV-2 susceptibility (a measure of the effectiveness of the UV light) in a buffer such as PBS was 4.4-fold greater than that in a cell culture medium. Furthermore, we discovered the attenuation of UVC disinfection by amino acids, vitamins, and niacinamide, highlighting the importance of determining UVC dosages under a condition close to aerosols that wrap the viruses. We developed a disinfection model to determine the effect of the environment on UVC effectiveness with three different wavelengths, 222 nm, 254 nm, and 265 nm. An inverse correlation between the liquid absorbance and the viral susceptibility was observed. We found that 222 nm light was most effective at reducing viral infectivity in low absorbing liquids such as PBS, whereas 265 nm light was most effective in high absorbing liquids such as cell culture medium. Viral susceptibility was further decreased in N95 masks with 222 nm light being the most effective. The safety of 222 nm was also studied. We detected changes to the mechanical properties of the stratum corneum of human skins when the 222 nm accumulative exposure exceeded 50 J/cm2.The findings highlight the need to evaluate each UV for a given application, as well as limiting the dose to the lowest dose necessary to avoid unnecessary exposure to the public.