Interaction between Foamy Macrophages and Smooth Muscle Cells in Atherogenesis in Rabbit Aortae: Lipoperoxidative Changes Occurring in Those Cells and Its Chemotactic Activity for Cell Migration.

Abstract

Macrophages (MΦs) and smooth muscle cells (SMCs) comprise atherosclerotic lesions and their migration, proliferation and foamy change are the essential steps in initiating and establishing the lesions. It is also a well-documented fact that the oxidatively modified LDLs (low density lipoproteins) play important roles involving various lipoperoxidative events in the migration and foamy change of those cells. Yet, detailed sequential cell processes in the atherosclerotic changes still remain unexplained. In the present study, the time related close spatial relationship of MΦs and SMCs in experimental rabbit atherosclerosis were histologically and immunohistochemically investigated. The MΦs' migration into the intima preceded the SMCs' migration. Migrated intimal SMCs encircle or enfold the foamy MΦs, and it appeared as if they were preventing MΦ migration. To confirm whether lipid peroxidation is involved in the migration and foamy change of MΦs or not, we performed immunohistochemical detection of the glutathione peroxidase (GSH-PO), a lipid peroxide scavenger, using the specific antibody against rabbit GSH-PO produced in our laboratory. Migrated foamy MΦs exhibited intense GSH-PO staining, suggesting the vigorous occurrence of lipid peroxidation. The cellular interaction between foamy MΦs and SMCs should be the essential factor in the pathogenesis of atherosclerosis.