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Atherosclerosis. 2008 Oct;200(2):239-46. doi: 10.1016/j.atherosclerosis.2008.03.025. Epub 2008 Apr 12.

Atherogenesis and the humoral immune response to modified lipoproteins.

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  • 1Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, United States. virellag@musc.edu

Abstract

Modified forms of LDL are immunogenic and activate both cell-mediated and humoral immune responses. Both types of responses are pro-inflammatory and are probably primary players in the perpetuation of the chronic inflammatory reaction characteristic of atherosclerosis. The immunologic response to modified LDL can be directed to MHC-II-associated peptides in the case of T helper cells, and to a variety of epitopes-modified lysine groups, modified phospholipids, proteins that become associated with oxidized LDL (such as beta2GP1)--in the case of B cell responses. T cell activation is likely to play a major role through cross-activation of macrophages. Humoral responses to modified LDL are pathogenic as a consequence of the formation of antigen-antibody complexes containing modified LDL and IgG antibodies. Those immune complexes induce cholesterol ester accumulation in macrophages and macrophage-like cells, and induce the release of pro-inflammatory cytokines, chemokines, oxygen active radicals, and matrix metalloproteinases from those cells. There is no conclusive evidence supporting a protective role for IgM antibodies in humans, possibly because autoantibodies to modified lipoproteins are predominantly of the IgG isotype.

PMID:
18513726
[PubMed - indexed for MEDLINE]
PMCID:
PMC2605965
Free PMC Article
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