Oxidised LDL modulates immune-activation by an IL-12 dependent mechanism.
Oxidised low density lipoprotein (oxLDL) is one factor that may cause the immune reaction in the artery wall characteristic of atherosclerosis. OxLDL can promote immune activation as determined by enhanced secretion of IFN-gamma and TNF by immune competent cells. We previously demonstrated that Platelet-activating factor (PAF)-like lipids and/or lysophosphatidylcholine (LPC) in OxLDL contribute significantly to this immune activation, but these factors may also inhibit immune activation, at higher concentrations. We here demonstrate that IL-12 induces enhanced IFN-gamma secretion in peripheral blood mononuclear cells (PBMC), with no addition of a specific antigen, as determined by ELISPOT. Antibodies to IL-12 and to MHC class II inhibited both IL-12- and oxLDL-induced IFN-gamma secretion. OxLDL induced IL-12 production in PBMC. In the presence of IL-10, a T helper 2 cytokine, oxLDL induced a decreased IFN-gamma secretion, indicating that the local cytokine-milieu may determine the immunological properties of oxLDL. IL-10 could also be induced by OxLDL. Mononuclear leukocytes were prepared directly from human atherosclerotic plaques obtained at carotid operations. OxLDL had the capacity to induce IL-12, IL-10 and TNF from plaque cells using ELISPOT. Taken together, our data indicate that oxLDL can modulate immune reactivity in atherosclerosis by a nonspecific mechanism. OxLDL can be inhibitory, especially at higher concentrations. However, oxLDL can also promote immune activation by functioning as an adjuvant, potentiating and/or modulating immune-reactions via IL-12 and other cytokines including IL-10. This suggests that a specific T cell epitope in oxLDL is not necessary for oxLDL-induced T cell activation.
Fei
Guo-Zhong
GZ
Department of Medicine, Karolinska Hospital, Karolinska Institute, S-17176 Stockholm, Sweden.
Huang
Yi Hui
YH
Swedenborg
Jesper
J
Frostegård
Johan
J
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001161:Arteriosclerosis / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D005802:Genes, MHC Class II / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008285:Major Histocompatibility Complex / Q000276:immunology; D008875:Middle Aged; D010084:Oxidation-Reduction
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D016207:Cytokines; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D018664:Interleukin-12; D007371:Interferon-gamma