Lipoprotein lipase in human plasma is mainly inactive and associated with cholesterol-rich lipoproteins.

This study was designed to further ascertain the presence in plasma of lipoprotein lipase (LPL) bound to circulating lipoproteins. Lipoprotein lipase mass and activity values in preheparin plasma from 20 volunteers were 69.8 +/- 6.6 ng.ml-1 and 1.54 +/- 0.15 mU.ml-1, respectively, and no significant correlation between mass and activity was observed. Fifteen min after heparin injection, LPL mass had increased to 536 +/- 60 ng.ml-1 and LPL activity to 261 +/- 34 mU.ml-1 and a highly significant correlation between the increments in mass and activity was observed. The released material had a specific activity of 0.57 +/- 0.03 mU.ng-1. The LPL mass in preheparin plasma eluted early from heparin-Sepharose, in the position expected for inactive LPL monomers. Western blot analysis showed that the eluted material had the size expected for the LPL subunit (55 kDa). The increment of mass and activity after heparin eluted later from heparin-Sepharose, in the position expected for active LPL dimers. It is concluded that preheparin plasma contains substantial amounts of inactive LPL protein, and that heparin releases mainly active LPL into circulation. On gel filtration LPL activity and mass in postheparin plasma eluted mainly in the positions of LDL and HDL. Electron microscopy of immunostained fractions showed reaction for LPL and apolipoprotein B, or apolipoprotein A-I, on the same particles. LPL mass in preheparin plasma eluted in a similar pattern, associated with LDL and HDL. In postprandial plasma substantial amounts of LPL protein eluted with the triglyceride-rich lipoproteins. When 125I-labeled bovine LPL was added to plasma or to ultracentrifugally isolated lipoproteins and then analyzed by gradient gel electrophoresis, the labeled lipase moved with the lipoproteins. The presence of substantial amounts of inactive LPL protein associated with lipoproteins in plasma may have important implications for the metabolism of the particles in view of recent reports on avid binding of LPL-lipoprotein complexes to cell surfaces and receptors.