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.
Virella
Gabriel
G
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, United States. virellag@musc.edu
Lopes-Virella
Maria F
MF
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