Absence of triglyceride accumulation in lipoprotein lipase-deficient human monocyte-macrophages incubated with human very low density lipoprotein.
Lipoprotein lipase, a lipolytic enzyme essential for normal hydrolysis of triglycerides in very low density lipoprotein (VLDL) and chylomicrons, is found in several cell types, including macrophages. The role of lipoprotein lipase in mediating the uptake of normal VLDL triglycerides into human cultured monocyte-derived macrophages was studied using macrophage cells from a functionally lipoprotein lipase-deficient patient and macrophages of cells from a normal subject. After incubation with VLDL, massive accumulation of phase refractile (lipid) inclusions were noted by phase contrast microscopy within the normal, but not within the lipoprotein lipase-deficient, macrophages. Chemical determinations of intracellular lipid confirmed massive triglyceride accumulation within normal macrophages, but not in lipoprotein lipase-deficient macrophages. VLDL-derived cholesterol did not accumulate in either cell. These results confirm an additional role of lipoprotein lipase, that of mediating triglyceride accumulation into macrophages from normal human VLDL. Human monocyte-macrophages genetically deficient in a functional lipoprotein lipase will be useful to determine the role of lipoprotein lipase in macrophage accumulation of lipid from other forms of triglyceride-carrying lipoproteins, including hypertriglyceridemic VLDL, beta-VLDL, and chylomicrons.
Skarlatos
S I
SI
Section of Experimental Atherosclerosis, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Dichek
H L
HL
Fojo
S S
SS
Brewer
H B
HB
Kruth
H S
HS
D000328:Adult; D005260:Female; D006801:Humans; D002479:Inclusion Bodies / Q000201:enzymology; D008071:Lipoprotein Lipase / Q000172:deficiency*; D008079:Lipoproteins, VLDL / Q000494:pharmacology*; D008264:Macrophages / Q000201:enzymology*; D008858:Microscopy, Phase-Contrast; D009000:Monocytes / Q000201:enzymology*; D014280:Triglycerides / Q000378:metabolism*
D008079:Lipoproteins, VLDL; D014280:Triglycerides; D008071:Lipoprotein Lipase