Components of the protein fraction of oxidized low density lipoprotein stimulate interleukin-1 alpha production by rabbit arterial macrophage-derived foam cells.

Oxidized low density lipoproteins (oxLDL) (0.5-50 pg/ml) generated from both rabbit and human LDL stimulated the production of interleukin-la (IL-la) by as much as 2- and 6-fold, respectively, as compared to native LDL after a 2-h incubation with macrophagederived foam cells isolated from the balloon-injured arteries of cholesterol- fed rabbits. Northern blot analyses confirmed that there was also an increase in the mRNA for IL-la and ILP in response to oxLDL in the isolated foam cells. The stimulation of IL-1 expression and production was not due to the contamination of the oxLDL preparations with endotoxin as neither the amount of endotoxin found to be associated with the lipopro- teins nor amounts up to 1 ng/ml stimulated IL-la produc- tion to the same degree as oxLDL. Neither oxidized P-very low density lipoprotein (VLDL) nor oxidized high density lipoprotein (HDL) stimulated IL-la production by the foam cells. Furthermore, acetyl-LDL had a very limited stimulatory effect, but other known ligands of the scavenger receptor such as maleylated-BSA, polyinosinic acid, and fucoidin elic- ited maximal IL-la responses. Fractionation of the oxLDL into lipid- and protein-soluble fractions showed that there was some stimulatory activity in the lipid phase but that known products of lipid peroxidation such as 9- and 13-HODE had no effect when added independently of lipoproteins. When added in combination with native LDL, only 13-HODE stimu- lated IL-la production. The delipidated apolipoprotein frag- ments of oxLDL that had been solubilized in P-octylglucoside stimulated the production of IL-la by the foam cells to a greater degree than the lipid extract, while reductively meth- ylated oxLDL did not. I These data suggest that interac- tions of components of both the lipid- and protein-soluble fractions of oxLDL with scavenger receptors or potentially with surface proteins that bind oxLDL may induce produc- tion of IL-1 by arterial macrophages.-Lipton, B. A., S. Parthasarathy, V. A. Ord, S. K. Clinton, P. Libby, and M. E. Rosenfeld. Components of the protein fraction of oxidized low density lipoprotein stimulate interleukin-la production by rabbit arterial macrophage-derived foam cells.). Lipid RPS. 1995.36: 2232-2242.