Tumor necrosis factor induced release of endothelial cell lipoprotein lipase.
The major functional pool of lipoprotein lipase (LPL) that hydrolyzes triglycerides in circulating lipoproteins is located on the vascular endothelium. The macrophage-secreted cytokine tumor necrosis factor (TNF), a molecule known to affect endothelial cell functions, was used to test the hypothesis that alterations of endothelial cell metabolism regulate the binding of LPL to these cells. TNF addition induced rapid (maximum release at 45 minutes) dissociation of LPL protein and activity from its binding sites on cultured porcine aortic endothelial cells. LPL release by TNF required endothelial cell metabolic event(s) which involved cell secretion. In addition, LPL release was inhibited by pertussis toxin, suggesting the involvement of guanine nucleotide regulatory protein(s). Addition of arachidonic acid, a molecule known to be released by endothelial cells due to phospholipase A2 activation by TNF treatment, released LPL from the cell surface. Furthermore, direct modulation of cellular phospholipase A2 activity also led to changes in the release of LPL. Our studies demonstrate that alterations in the cellular metabolism of endothelial cells, for example, by TNF, may release functional pools of LPL from the vascular endothelium. This decrease in LPL on endothelial cell surfaces might be involved in the development of hypertriglyceridemia and redirection of energy flow during infections and inflammation.
Saxena
U
U
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032.
Witte
L D
LD
Goldberg
I J
IJ
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000096:biosynthesis; D015777:Eicosanoids / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology*; D006025:Glycosaminoglycans / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism*; D010741:Phospholipases A / Q000502:physiology; D054467:Phospholipases A2; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D013696:Temperature; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D001095:Arachidonic Acids; D015777:Eicosanoids; D006025:Glycosaminoglycans; D010982:Platelet-Derived Growth Factor; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D010741:Phospholipases A; D008071:Lipoprotein Lipase; D054467:Phospholipases A2