Immunoglobulin treatment reduces atherosclerosis in apo E knockout mice.

Abstract

Atherosclerosis is associated with immune activation. T cells and macrophages infiltrate atherosclerotic plaques and disease progression is associated with formation of autoantibodies to oxidized lipoproteins. In the apo E knockout mouse, a genetic model of cholesterol-induced atherosclerosis, congenital deficiency of macrophages, lymphocytes, or interferon-␥ receptors result in reduced lesion formation. We have now evaluated whether immune modulation in the adult animal affects disease development. Injections of 7-wk-old male apo E knockout mice with polyclonal immunoglobulin preparations (ivIg) during a 5-d period reduced fatty streak formation over a 2-mo period on cholesterol diet by 35%. Fibrofatty lesions induced by diet treatment for 4 mo were reduced by 50% in mice receiving ivIg after 2 mo on the diet. ivIg treatment also reduced IgM antibodies to oxidized LDL and led to inactivation of spleen and lymph node T cells. These data indicate that ivIg inhibits atherosclerosis, that it is effective both during the fatty streak and plaque phases, and that it may act by modulating T cell activity and/or antibody production. Therefore, immunomodulation may be an effective way to prevent and/or treat atherosclerosis. ( J. Clin. Invest. 1998. 102:910-918.)

Recombinant Human Antibodies Against Aldehyde-Modified Apolipoprotein B-100 Peptide Sequences Inhibit Atherosclerosis

“…Support for the existence of atheroprotective humoral immunity also comes from studies in apoE Ϫ/Ϫ mice demonstrating inhibi- tion of atherosclerosis by repeated injections of polyclonal IgG and by B-cell rescue of splenectomized mice. 18,19 The mouse model of atherosclerosis used in this study has some limitations when it comes to analyzing the effect of human antibodies against human oxLDL epitopes. Homology to the corresponding mouse apoB-100 sequences is not complete (95%), and the sequence recognized by the KTT antibodies is not expressed in the majority of mouse LDL particles in apoE Ϫ/Ϫ mice, because most of these are carrying apoB-48.…”

Liver X receptors in the central nervous system: From lipid homeostasis to neuronal degeneration

“…For myelin staining, the black-gold method was used as described (24). Lipid deposits were revealed by staining with oil red O on cryosections as previously described (25). To compare the ultrastructure of microvessels, microglia, neurons, and astrocytes of wild-type and LXR␣ Ϫ/Ϫ ␤ Ϫ/Ϫ mice, several regions, including cerebral cortex, hippocampus, caudate putamen, globus pallidus, substantia nigra, cerebellum, lateral ventricle, third ventricle, and spinal cord, were cut as 0.8-m semithin sections and stained with toluidine blue.…”

The Lamina Adventitia Is the Major Site of Immune Cell Accumulation in Standard Chow-Fed Apolipoprotein E–Deficient Mice

“…Every tenth section was stained with oil red O. Areas from 8 consecutive oil red O-stained sections were measured using Leica Q500/W software and both the surface area of lesions 34 ; the intima/media (I/M) ratio 35 and the fraction area of lesions (FA) 36 were calculated.…”