LIPOPROTEIN-LIPASE REGULATES FC RECEPTOR-MEDIATED PHAGOCYTOSIS BY MACROPHAGES MAINTAINED IN GLUCOSE-DEFICIENT MEDIUM

During periods of intense activity such as phagocytosis, macrophages a re thought to derive most of their energy from glucose metabolism unde r both aerobic and anaerobic conditions. To determine whether fatty ac ids released from lipoproteins by macrophage Lipoprotein lipase (LPL) could substitute for glucose as a source of energy for phagocytosis, w e cultured peritoneal macrophages from normal and LPL knockout (LPL-KO ) mice that had been rescued from neonatal demise by expression of hum an LPL via the muscle creatine kinase promoter, Normal and LPL-KO macr ophages were cultured in medium containing normal (5 mM) or low (1 mM) glucose, and were tested for their capacity to phagocytose IgG-opsoni zed sheep erythrocytes. LPL-KO macrophages maintained in 1 and 5 mM gl ucose phagocytosed 67 and 798 fewer IgG-opsonized erythrocytes, respec tively, than macrophages from normal mice. Addition of VLDL to LPL-exp ressing macrophages maintained in 1 mM glucose enhanced the macrophage s' phagocytosis of IgG-opsonized erythrocytes, but did not stimulate p hagocytosis by LPL-KO macrophages. Inhibition of secreted LPL with a m onoclonal anti-LPL antibody or with tetrahydrolipstatin blocked the ab ility of VLDL to enhance phagocytosis by LPL-expressing macrophages ma intained in 1 mM glucose, Addition of oleic acid significantly enhance d phagocytosis by both LPL-expressing and LPL-KO macrophages maintaine d in I mM glucose. Moreover, oleic acid stimulated phagocytosis in cel ls cultured in non-glucose-containing medium, and increased the intrac ellular stores of creatine phosphate. Inhibition of oxidative phosphor ylation, but not of glycolysis, blocked the capacity of oleic acid to stimulate phagocytosis. Receptor-mediated endocytosis of acetyl LDL by macrophages from LPL-expressing and LPL-KO mice was similar whether t he cells were maintained in 5 or 1 mM glucose, and was not augmented b y VLDL. We postulate that fatty acids derived from macrophage LPL-cata lyzed hydrolysis of triglycerides and phospholipids provide energy for macrophages in areas that have limited amounts of ambient glucose, an d during periods of intense metabolic activity.