Atherogenesis and the humoral immune response to modified lipoproteins.
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.
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, United States. virellag@musc.edu
Gabriel
G
Virella
Maria F
MF
Lopes-Virella
D000818:Animals; D000917:Antibody Formation / Q000502:physiology*; D050197:Atherosclerosis / Q000473:pathology*; D001323:Autoantibodies / Q000276:immunology; D018925:Chemokines / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D007074:Immunoglobulin G / Q000737:chemistry; D007249:Inflammation; D008074:Lipoproteins / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D051379:Mice; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism
D001323:Autoantibodies; D018925:Chemokines; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D008074:Lipoproteins; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein