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 atherogenesis 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 selective protein oxidant, or copper sulfate (CuSO(4)), a major lipid oxidant, and tested for their capacity to activate the NADPH-oxidase of human THP-1- and U937-derived macrophages as measured by lucigenin chemiluminescence (CL). 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 differentiated into macrophages by phorbol myristate acetate. In contrast, Cu-oxLDL only triggered a moderate CL response of U937 cells and had little effect on THP-1 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 finding which could be related to their higher expression of the scavenger receptor CD36. Taken together these results strongly support the role of the protein moiety in oxLDL-induced macrophage activation.
Nguyen-Khoa
T
T
INSERM U507, Necker Hospital, Paris, France.
Massy
Z A
ZA
Witko-Sarsat
V
V
Canteloup
S
S
Kebede
M
M
Lacour
B
B
Drüeke
T
T
Descamps-Latscha
B
B
D015703:Antigens, CD / Q000032:analysis / Q000235:genetics; D018955:CD36 Antigens / Q000032:analysis / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D003300:Copper; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood*; D006997:Hypochlorous Acid; D008077:Lipoproteins, LDL / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D008163:Luminescent Measurements; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D019255:NADPH Oxidases / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D020298:U937 Cells
D015703:Antigens, CD; D018955:CD36 Antigens; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D006997:Hypochlorous Acid; D003300:Copper; D019255:NADPH Oxidases; D013755:Tetradecanoylphorbol Acetate