Hauton David, Evans Rhys D
Nuffield Department of Anaesthetics, University of Oxford, Radcliffe Infirmary, United Kingdom.
Cell Physiol Biochem. 2002;12(5-6):293-304. doi: 10.1159/000067899.
BACKGROUND/AIMS: Plasma very-low-density lipoprotein (VLDL) concentrations are increased during sepsis/endotoxaemia and VLDL may be substrates for the activated immune system. Lipid substrate utilisation by quiescent and activated macrophages was therefore examined.
Rat R2 macrophages were incubated with oleate or rat VLDL, with or without lipopolysaccharide (LPS) stimulation. The metabolic fate of the lipids was examined.
Macrophages utilised both oleate and (control) VLDL-triacylglycerol (TAG) to a similar extent. Most was deposited as cellular lipid; about 10% of oleate was oxidised compared to 25% of cVLDL-TAG. LPS significantly increased oleate oxidation and its deposition as cellular lipid (mostly as TAG) at 48hrs but abolished both oxidation and storage of VLDL-TAG. VLDL produced during endotoxaemia (eVLDL) was assimilated by the unstimulated macrophage to a greater extent than oleate or cVLDL-TAG and selectively stored as cellular lipids (no oxidation); LPS decreased eVLDL utilisation. VLDL-TAG utilisation was decreased by the lipoprotein lipase (LPL) inhibitor terahydrolipstatin. LPL activity was greater in oleate than in VLDL incubations, but was increased by incubation with eVLDL. LPS had no effect (oleate, cVLDL) or increased (eVLDL) LPL activity.
VLDL represented an efficient substrate for the macrophage. However under conditions of sepsis/endotoxaemia eVLDL utilisation was limited and directed away from oxidation, suggesting that the increased plasma TAG (eVLDL) concentrations resulting from sepsis is not a respiratory fuel for the macrophage but may supply cellular lipid.
背景/目的：脓毒症/内毒素血症期间血浆极低密度脂蛋白（VLDL）浓度升高，且VLDL可能是被激活的免疫系统的底物。因此，研究了静止和激活的巨噬细胞对脂质底物的利用情况。
将大鼠R2巨噬细胞与油酸或大鼠VLDL一起孵育，同时给予或不给予脂多糖（LPS）刺激。检测脂质的代谢去向。
巨噬细胞对油酸和（对照）VLDL-三酰甘油（TAG）的利用程度相似。大部分脂质沉积为细胞内脂质；约10%的油酸被氧化，而cVLDL-TAG的氧化率为25%。LPS显著增加了48小时时油酸的氧化及其作为细胞内脂质（主要为TAG）的沉积，但消除了VLDL-TAG的氧化和储存。内毒素血症期间产生的VLDL（eVLDL）被未刺激的巨噬细胞摄取的程度高于油酸或cVLDL-TAG，并选择性地储存为细胞内脂质（无氧化）；LPS降低了eVLDL的利用。脂蛋白脂肪酶（LPL）抑制剂四氢脂抑素降低了VLDL-TAG的利用。油酸孵育时LPL活性高于VLDL孵育，但与eVLDL孵育可增加LPL活性。LPS对LPL活性无影响（油酸、cVLDL）或增加（eVLDL）。
VLDL是巨噬细胞的有效底物。然而，在脓毒症/内毒素血症条件下，eVLDL的利用受到限制且不用于氧化，这表明脓毒症导致的血浆TAG（eVLDL）浓度升高不是巨噬细胞的呼吸燃料，但可能提供细胞内脂质。
