Pathogenetic Significance of Lipid Peroxidation in Various Cell Injuries, with a Special Reference to the Investigation on Cell Biological Characteristics of Glutathione Peroxidase-an Anti-lipoperoxidative Agent.

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Through a series of the experiments on lipoperoxidative cell injury or the enhanced lipid peroxidation in hepatocytes and peritoneal macrophages (M ), it was proved that the lipid peroxidation of certain degree elicited the increase of the glutathione peroxidase (GSH-PO), the effective lipid peroxides scavenger, in those cells. The other way around, the increase of GSH-PO synthesis in certain cell would strongly suggest that the increased lipid peroxidation may have been induced in those cells. On the basis of this notion, the immunohistochemical localization of GSH-PO in the atherosclerotic lesions of human arteries was investigated utilizing the anti human GSH-PO prepared in our laboratory after its immunohistochemical validity was checked by "Western" immunoblotting test. As a results, GSH-PO was specifically localized in "foamy cells" which are supposed to be originated from both the infiltrating M s and the intimal smooth muscle cells (SMC). Degenerated and/or deformed SMCs which are precursor to the "foamy cell" also showed the intense immunoperoxidase staining for the GSH-PO. Non-atherosclerotic arteries did not show such GSH-PO immunoperoxidase staining except the very weak staining shown in SMCs in their media.In order to examine the course and the causative stimulation of the above changes, rabbits were fed with the high cholesterol diet (Oriental-Kohbo Co. Led) which was proved to induce typical atherosclerotic changes in their arteries for sure. The initial GSH-PO appeorance was observed in the foamy M s lined just beneath the endothelial cells in a monolayer. 2 weeks after the initiation of the diet. Sequentially, such GSH-PO positive cells increased their number, and GSH-positive SMCs gave their first appearance at 4th to 8th week.Summerizing these results, the pathogenetic significance of the lipid peroxidation taking place in those "foamy cells" for atherosclerosis was stressed.