Isolation of macrophage-like cell mutants resistant to the cytotoxic effect of oxidized low density lipoprotein.
A high concentration of oxidized low density lipoprotein (Ox-LDL) showed a cytotoxic effect on mouse macrophage-derived J774 cells. Mutant cells were selected from these cells that were resistant to the cytotoxic effect of Ox-LDL. One mutant form, named JO21b cells, was characterized in the present study. In spite of a marked resistance to the cytotoxic effect of Ox-LDL, JO21b cells were apparently as sensitive as the parent cells not only to toxic moieties of Ox-LDL, such as 7-ketocholesterol and lysophosphatidylcholine, but also to t-butyl hydroperoxide, an artificial lipid hydroperoxide analog. However, the cellular association of 125I-labeled Ox-LDL with, and subsequent endocytic degradation by JO21b cells was reduced by 70-80% compared with J774 cells. Similarly, accumulation of cholesteryl esters in JO21b cell by Ox-LDL was also reduced by 70%. Northern blot analyses of type I and type II macrophage scavenger receptors (type I and type II MSR) demonstrated that the mRNA levels of JO21b cells were lower than those of J774 cells. Moreover, peritoneal macrophages obtained from MSR-knockout mice showed a higher resistance to the cytotoxic effect of Ox-LDL than those from their wild-type littermates. Our results suggest, therefore, that macrophage scavenger receptor-mediated endocytic uptake of oxidized low density lipoproteins (Ox-LDL) may play an enhancing role in Ox-LDL cytotoxicity to macrophages or macrophage-derived cells.[1]References
- Isolation of macrophage-like cell mutants resistant to the cytotoxic effect of oxidized low density lipoprotein. Hakamata, H., Miyazaki, A., Sakai, M., Matsuda, H., Suzuki, H., Kodama, T., Horiuchi, S. J. Lipid Res. (1998) [Pubmed]
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