Oxidized low-density lipoprotein induces macrophage respiratory burst via its protein moiety: A novel pathway in atherogenesis?

Oxidized low-density Lipoproteins (oxLDL) play a crucial role in atherogene sis mainly via their capacity to bind and to activate macrophages, However, the role of the protein LDL moiety in this process is not yet established. In this study, human LDL were exposed to hypochlorous acid (HOCl), a selec tive protein oxidant, or copper sulfate (CuSO4), a major lipid oxidant, and tested for their capacity to activate the NADPH-oxidase of human THP-1- an d U937-derived macrophages as measured by lucigenin chemiluminescence (GL). Compared to native LDL which had no effect, HOCl-oxLDL triggered potent CL responses in both U937 and THP-1 cells but only when these were fully diff erentiated into macrophages by phorbol myristate acetate, In contrast, Cu-o xLDL only triggered a moderate CL response of U937 cells and had little eff ect on THP-I cells. While delipidation did not affect HOCl-oxLDL-induced CL response it abolished that induced by Cu-oxLDL. Interestingly, U937 cells showed higher CL responses to both types of oxLDL than THP-1 cells, a findi ng which could be related to their higher expression of the scavenger recep tor CD36. Taken together these results strongly support the role of the pro tein moiety in oxLDL-induced macrophage activation. (C) 1999 Academic Press .