Endogenously produced glycosaminoglycans affecting the release of lipoprotein lipase from macrophages and the interaction with lipoproteins.
Macrophages are intimately involved in the pathogenesis of atherosclerotic diseases. A key feature of this process is their uptake of various lipoproteins and subsequent transformation to foam cells. Since lipoprotein lipase (LPL) is believed to play a role in foam cell formation, we investigated if endogenously produced proteoglycans (PGs) affect the release of this enzyme from macrophages. The human leukaemic cell line THP-1 which differentiates into macrophages by treatment with phorbol ester (phorbol 12-myristate 13-acetate) served as a model. The differentiation of THP-1 macrophages promoted the release of PGs into the cell medium which caused the detachment of LPL activity from the cell surface, and prevented LPL re-uptake and inactivation. These PGs were mainly composed of chondroitin sulfate type and exerted a heparin-like effect on LPL release. LPL is known to increase the cell association of lipoproteins by the well known bridging function. Exogenous bovine LPL at a concentration of 1 microg/ml enhanced low density lipoprotein (LDL)-binding 10-fold. Endogenously produced PGs reduced LPL-mediated binding of LDL. It is proposed that the differentiation-dependent increase in the release of PGs interferes with binding of LPL and reduces lipoprotein-binding to macrophages.
Zimmermann
R
R
Institute of Medical Biochemistry, University of Graz, Harrachgasse 21/3, A-8010, Graz, Austria.
Sartipy
P
P
Winkler
R
R
Zechner
R
R
Hurt-Camejo
E
E
Kostner
G M
GM
D001161:Arteriosclerosis / Q000378:metabolism; D002460:Cell Line; D002809:Chondroitin Sulfates / Q000378:metabolism; D017077:Culture Media, Conditioned; D003871:Dermatan Sulfate / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism* / Q000494:pharmacology; D008074:Lipoproteins / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D011509:Proteoglycans / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*
D017077:Culture Media, Conditioned; D006025:Glycosaminoglycans; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D011509:Proteoglycans; D003871:Dermatan Sulfate; D006493:Heparin; D002809:Chondroitin Sulfates; D008071:Lipoprotein Lipase