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- W1088082165 abstract "NM is a vesicant known to target the lung, causing acute injury which progresses to fibrosis. Evidence suggests that macrophages (MPs) contribute to the development of lung fibrosis. In these studies, we characterized MPs in the lung during the development of NM-induced fibrosis and assessed whether phenotypic changes in these cells is associated with altered lipid metabolism. Following exposure of rats to NM (0.125 mg/kg, i.t.), there was a time-related accumulation of MPs in the lung expressing CD68 and CD163, scavenger receptors important in uptake of oxidized lipoproteins; this was noted beginning at 3 d and continuing for at least 28 d, a response coordinated with the development of fibrosis. At 28 d, lung MPs were enlarged and foamy, and stained positive for oil red O, an indication of intracellular lipids. This was associated with an early (1-3 d) decrease in bronchoalveolar lavage phospholipid content followed by an increase at 7 d and 28 d. Liver X receptor (LXR) is a transcription factor regulating expression of scavenger receptors and lipid synthesis, metabolism and homeostasis. Three d post NM, LXR expression transiently decreased in lung MPs; this was correlated with a decrease in cholesterol efflux transporters (ABCA and ABCG) which are targets of LXR. Conversely, a time-related increase was observed in CD36 and ApoE, LXR targets important in binding and clearance of oxidized lipoproteins, respectively and accumulation of oxLDL in MPs, while LXR targets involved in cholesterol synthesis (ACAT, CYP27A1, LDLR) were unaltered. These data suggest that NM induces alterations in lipid metabolism resulting in lipoprotein accumulation in macrophages and foam cell formation. NIH AR055073, HL096426, ES004738 & ES005022." @default.
- W1088082165 created "2016-06-24" @default.
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- W1088082165 date "2015-04-01" @default.
- W1088082165 modified "2023-10-17" @default.
- W1088082165 title "Nitrogen Mustard (NM)‐induced Lung Fibrosis is Associated with Altered Lipid Metabolism and Foam Cell Formation" @default.
- W1088082165 doi "https://doi.org/10.1096/fasebj.29.1_supplement.774.2" @default.
- W1088082165 hasPublicationYear "2015" @default.
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