抄録
In order to elucidate the role of macrophages in atherosclerosis, sequential observations of cholesterol-induced rabbit aortic lesions were preformed by the immunoperoxidase technique using anti-monocyte-macrophage monoclonal antibody named SRM1.
Animals on the cholesterol diet for 8 weeks or longer showed increased accumulations of lipidfilled, SRM1 positive macrophages in the subendothelial space. In early stages in which no grossly visible alteration was manifested, macrophages with or without lipid vaculoes could be seen clinging to the endothelial surface and apparently penetrating the endothelium. A single line of 3 or 4 vacuolated macrophages was found in otherwise almost normal subendothelial zone, and, in flat lesions consisted of a few layers of foam cells, lipid-laden macrophages were cells predominated. It could be therefore indicated that circulating monocytes are the prime source of foam cells in these early fatty lesions.
After 16 weeks of cholesterol feeding intimal lesions further progressed. In advanced plaque lesions SRM1 negative, smooth muscle foam cells became remarkable and tended to be numerous in places. In these lesions, macrophage foam cells were predominated in the superficial layer and often arranged in a row under the endothelium, whereas smooth muscle foam cells were prevalent in the deeper areas. In addition, SRM1 negative, elongated cells were scattered throughout the lesion. In atheroma lesions SRM1 positive macrophages were notably seen within the area of necrosis, and, later, situated occasionally near the necrotic core of the atheroma. In addition, they were preferentially observed in the vicinity of SRM1 negative foam cells still lying in fibrous plaque leions; the spatial relationship of macrophages to SRM1 negative foam cells thus gave an impression that disintegration of the latter cells was apparently a nidus of activity.
After stopping the cholesterol diet, numbers of SRM1 positive macrophages in the atheroma lesion diminished remarkably, and SRM1 positive cells actually breaching the endothelium almost totally disappeared.
It seems likely that the defined role of macrophages in atherogenesis is to remove lipid from areas of lesion formation. The removal of lipid by macrophages, however, is not always so efficient to prevent medial cell involvement that, in a protracted course of hyperlipemia, fatty streak lesion may progress to advanced ones. The slow or absent resorption of lipid from atheromatous lesions may in part be attributed to the paucity of macrophages therein.
