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Abstract-Heterogeneity of peripheral blood monocytes is characterized by specific patterns in the membrane expression of Fc ␥-receptor III (Fc␥RIII/CD16) and the lipopolysaccharide receptor (LPS receptor CD14), allowing discrimination of distinct subpopulations. The aim was to analyze the correlation of these phenotypic differences to the early interaction of freshly isolated monocytes with modified lipoproteins by the use of either enzymatically degraded low density lipoprotein (E-LDL), acetylated low density lipoprotein (ac-LDL), oxidized low density lipoprotein (ox-LDL), or native low density lipoprotein. Highest E-LDL binding was observed on CD14 high CD16 ϩ monocytes as determined by flow cytometry, suggesting a selective interaction of E-LDL with distinct subpopulations of monocytes. E-LDL induced rapid foam cell formation both in predifferentiated monocyte-derived macrophages and, in contrast to ac-LDL or ox-LDL, also in freshly isolated peripheral blood monocytes. This was accompanied by upregulation of the 2 class B scavenger receptors CLA-1/SR-BI (CD36 and LIMPII Analogous-1/scavenger receptor type B class I) and CD36. Cellular binding and uptake of E-LDL was neither competed by ac-LDL nor the class A scavenger-receptor inhibitor polyinosinic acid but was partially inhibited by an excess of ox-LDL. In predifferentiated monocyte-derived macrophages, an anti-CD36 antibody inhibited cellular binding and uptake of E-LDL by Ϸ20%, suggesting that recognition of these hydrolasemodified low density lipoprotein particles is mediated only in part by the class B scavenger receptor CD36. Peripheral blood monocytes are phenotypically different with respect to membrane expression of Fc ␥-receptor III (Fc␥RIII/CD16) and the lipopolysaccharide receptor (LPS receptor/CD14), allowing discrimination of distinct subpopulations. 1 The impact on atherogenicity is as yet unknown. Within the vessel wall, the transformation of monocytes to macrophage foam cells may derive from the cellular uptake of different forms of chemically modified lipids and lipoproteins. Partial hydrolysis of lipoproteins by the hydrolytic host defense machinery, such as enzymatically degraded LDL (E-LDL), transforms lipoproteins to an atherogenic moiety. [2][3][4] Other lipoprotein modifications considered as relevant in atherogenesis include oxidized LDL (ox-LDL), 5 advanced glycation end products, 6 LDL modified by phospholipase A 2 , 7 and aggregated LDL. 8 Cellular uptake of these lipids and lipoproteins is considered to be mediated by charge and motif receptors directly recognizing nonopsonized ligands.Despite increasing knowledge about the mechanisms involved in foam cell formation of predifferentiated monocytederived macrophages, little is known about the interaction of freshly isolated monocytes with modified lipoproteins. In the present study, we demonstrate the correlation of blood monocyte heterogeneity to the cellular interaction with E-LDL. Furthermore, the present study shows that E-LDL, compared with acetylated LDL (ac-LDL) and ox-LDL, ...

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