Enzymatically degraded LDL preferentially binds to CD14(high) CD16(+) monocytes and induces foam cell formation mediated only in part by the class B scavenger-receptor CD36

Heterogeneity of peripheral blood monocytes is characterized by specific pa tterns in the membrane expression of Fc gamma -receptor III (Fc gamma RIII/ CD16) and the lipopolysaccharide receptor (LPS receptor CD14), allowing dis crimination of distinct subpopulations. The aim was to analyze the correlat ion of these phenotypic differences to the early interaction of freshly iso lated monocytes with modified lipoproteins by the use of either enzymatical ly degraded low density lipoprotein (E-LDL), acetylated low density lipopro tein (ac-LDL), oxidized low density lipoprotein (ox-LDL), or native low den sity lipoprotein. Highest E-LDL binding was observed on CD14(high) CD16(+) monocytes as determined by flow cytometry, suggesting a selective interacti on 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 b lood monocytes. This was accompanied by upregulation of the 2 class B scave nger 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 polyinosin ic acid but was partially inhibited by an excess of ox-LDL. In predifferent iated monocyte-derived macrophages, an anti-CD36 antibody inhibited cellula r binding and uptake of E-LDL by approximate to 20%, suggesting that recogn ition of these hydrolase-modified low density lipoprotein particles is medi ated only in part by the class B scavenger receptor CD36.