Role of lipid peroxidation in the inhibition of mononuclear cell proliferation by normal lipoproteins.
Stimulated peripheral blood mononuclear cells (PBMC) can oxidize normal lipoproteins, and sufficiently oxidized lipoproteins are cytotoxic. However, the role of lipid peroxidation in the inhibition of mitogen-stimulated PBMC proliferation by physiologic concentrations of normal lipoproteins is unclear. In the present investigation, normal low density lipoprotein (LDL) and very low density lipoprotein (VLDL) suppressed [3H]thymidine incorporation and gamma interferon production in concanavalin A-stimulated PBMC without causing cell death. This suppression was accompanied by parallel increases in lipid peroxidation products measured as thiobarbituric acid reactive substances (TBARS). In contrast, high density lipoprotein (HDL) failed to inhibit PBMC and TBARS remains low. Differences between the PBMC suppression from LDL, VLDL, and HDL were best accounted for by normalizing the lipoprotein concentrations by their total lipid content. Moreover, the antioxidants superoxide dismutase and butylated hydroxytoluene each substantially ameliorated the inhibition of PBMC caused by LDL, and reduced the levels of lipid peroxidation products that were generated. Altogether, these results suggest that reactive oxygen species generated by stimulated PMBC may cause oxidative alterations of normal lipoproteins that may, in turn, account for much of the previously reported inhibition of PBMC by normal lipoproteins.
Kasiske
B L
BL
Department of Medicine, University of Minnesota College of Medicine, Hennepin County Medical Center, Minneapolis 55415.
Keane
W F
WF
D000975:Antioxidants; D002455:Cell Division; D002478:Cells, Cultured; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology*; D015227:Lipid Peroxidation; D008074:Lipoproteins / Q000378:metabolism / Q000502:physiology*; D008075:Lipoproteins, HDL / Q000378:metabolism / Q000502:physiology; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000502:physiology; D013936:Thymidine / Q000378:metabolism
D000975:Antioxidants; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D007371:Interferon-gamma; D013936:Thymidine