Biochemical and Immunological Evidence for the Presence of Lipoprotein-Antilipoprotein Immune Complexes in Human Atherosclerotic Plaques

  • William Hollander
  • Antonio Lazzari
  • Carl Franzblau
Conference paper


Previous immunohistochemical studies of human atherosclerotic plaques have indicated a close association of the lipid protein complexes with the immunoglobulins (IgA, IgG, IgM) and complement (C3) contained in the lesion. The aim of the present studies was to determine whether the lipid-protein complexes or altered lipoproteins contained in the atherosclerotic plaque are present in the form of lipoprotein-antibody immune complexes.

The lipid-protein complexes were extracted from aortic atherosclerotic plaques into phosphate buffered saline and separated in the ultracentrifuge into a very low density fraction of d < 1.006 g/mL (VLDF) and a low density fraction of d 1.063–1.006 g/mL (LDF). LDF and VLDF were then purified by gel filtration on a Bio-Gel A-150 m column. The fractions were rich in cholesteryl ester and contained immunoreactive apo A-I, B, C-III and E as well as IgG, IgM, and C3. Small amounts of glycosaminoglycans (GAGs) consisting mainly of hyaluronic acid and chondroitin sulfate-C were detected in the fractions as was calcium. When examined by scanning electron microscope LDF and VLDF appeared heterogeneous in size and shape and showed surface irregularities and defects consistent with the appearance of aggregated and degraded lipoproteins. When mouse peritoneal macrophages were incubated with LDF or VLDF, they accumulated cholesterol and cholesteryl ester and became foam cells. In contrast to the macrophages, smooth muscle cells did not accumulate lipid when incubated with LDF or VLDF. The uptake of the lipid-protein complexes by the macrophage appeared to be mediated by the protein component of the complexes since pretreatment of LDF or VLDF with pronase completely inhibited lipid deposition in the macrophage. Digestion of LDF or VLDF with chondroitinase ABC and hyaluronidase removed the GAG components of the complexes but it did not reduce lipid accumulation in the macrophage suggesting that the uptake of the complexes is not mediated by the dextran sulfate receptors of the macrophage. Competitive inhibition studies with opsonized sheep red blood cells suggest that the immune receptors (Fc and C3b receptors) of the macrophage may mediate the uptake of LDF and VLDF in a manner similar to that of an immune complex. The protein composition of foam cells isolated from atherosclerotic plaques, as revealed by immunohistochemical examination, appeared to be similar to that of the lipid-protein complexes and mouse peritoneal macrophages pre-incubated with these complexes suggesting that the complexes may play a role in the formation of macrophage derived foam cells in atherosclerotic lesions. The overall results of the study suggest that the lipid-protein complexes, which account for over 90% of the lipoprotein fractions isolated from atherosclerotic lesions, are altered plasma lipoproteins which have the biochemical and biological behavior of a lipoprotein-antibody immune complex.


Atherosclerotic Plaque Cholesteryl Ester Peritoneal Macrophage Foam Cell Mouse Peritoneal Macrophage 
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Copyright information

© Springer-Verlag New York Inc. 1990

Authors and Affiliations

  • William Hollander
  • Antonio Lazzari
  • Carl Franzblau

There are no affiliations available

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