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 lipoprot eins 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 enzym e from macrophages. The human leukaemic cell line THP-1 which differentiate s into macrophages by treatment with phorbol eater (phorbol 12-myristate 13 -acetate) served as a model. The differentiation of THP-1 macrophages promo ted 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 inactiv ation. These PGs were mainly composed of chondroitin sulfate type and exert ed 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 mu g/ml enhanced low density lipoprotein (LDL)-binding 10-fold. Endogenously produced PGs reduced LPL-mediated bind ing of LDL. It is proposed that the differentiation-dependent increase in t he release of PGs interferes with binding of LPL and reduces lipoprotein-bi nding to macrophages. (C) 2000 Elsevier Science B.V. All rights reserved.