[Proatherogenic effects of immune complexes of human oxLDL in vitro].
OBJECTIVE
To observe the effects of immune complexes (IC) prepared from human oxidized density lipoprotein (oxLDL) antibodies and human oxLDL on the foam cell forming and the macrophage activation, and to further uncover the possible mechanisms of immune complexes contributing to the atherosclerosis occurrence.


METHODS
The immune complexes of human oxLDL and purified human oxLDL antibodies were added to culture U937 cells by protocols: polyethylene glycol-precipitated insoluble IC (PEG-IC) and IC immobilized by absorption to red blood cells (RBC-IC). With oxLDL as controls and heat-aggregated gamma globulin as an inhibitor of Fc gamma receptor, we measured the cholesterol ester, total cholesterol of the cellular extracts, and quantified the secreted MMP-1 of supernatants from U937 cells.


RESULTS
A significant increase of MMP-1 release [(0.769 +/- 0.030) ng/ml vs (0.513 +/- 0.034) ng/ml, P < 0.01] and a higher level of cholesterol ester accumulation [(20.271 +/- 1.668) microg/mg protein vs (17. 226 +/- 1.298 ) microg/mg protein, P < 0.05] in U937 cells incubated with RBC-IC were observed, compared with those incubated with RBC-oxLDL. However, the above quantative difference between the cholesterol ester accumulation induced by oxLDL and insoluble PEG-IC was even more striking, and cholesterol ester accumulation was dosage-dependent. Heat-aggregated gamma globulin (10 mg/ml) as an inhibitor of Fc gamma receptors competitively inhibited cholesterol ester accumulation and decreased PEG-IC stimulating MMP-1 secretion to 71%.


CONCLUSIONS
Immune complexe of ox-LDL can transform macrophages into foam cells and activted macrophages. The immunological function of oxLDL is involved in the process of atherosclerosis occurrence.
Liang
Zhong-shu
ZS
Department of Cardiology, Third Xiangya Hospital, Central South University, Changsha 410013, China. liangzshchina@163.com
Yang
Kan
K
Cao
Yu
Y
Ou-Yang
Mao
M
Zhang
Zhi-hui
ZH
Li
Jing-le
JL
Tang
Xiao-hong
XH
Zhang
Meng-xi
MX
D000906:Antibodies / Q000494:pharmacology; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D005487:Foam Cells / Q000187:drug effects; D006801:Humans; D008077:Lipoproteins, LDL / Q000276:immunology* / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis*; D020298:U937 Cells
D000906:Antibodies; D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D020781:Matrix Metalloproteinase 1