The cellular origin and development of early intimal lesions of rabbits fed a cholesterol diet for 8 to 12 weeks were studied morphologically and analyzed for several features of macrophage properties.Scanning and transmission electron microscopic observations demonstrated a large number of circulating cells attached to the endothelial surface and the number of these which appeared to be migrating across the endothelium. Early fatty lesions were characterized by accumulations of fat-filled foam cells in the intima accompanied by appreciable numbers of blood-derived cells, notably monocytes, lymphocytes and polymorphonuclear leukocytes. Transitional sequences from the monocytes to the lipid-containing macrophages or foam cells were discerned. According to the method of Schaffner et al., foam cells were isolated from suspensions by substrate adherence to analyze the presence of authentic Fc and C3 receptors, immune or nonimmune phagocytic capacity, or to perform cytochemical examination. Easily dislodged plastic-adherent cells were filled with oil red O-positive granules and showed remarkable staining for nonspecific esterase. More than 90% of these plasticadherent cells had Fc receptors, whereas about 80% of them possessed C3 receptors. Attached erythrocytes were rapidly phagocytized. Ultrastructural observation of rosette-forming cells confirmed several features compatible with foam cells derived from macrophages. In addition, these cells exhibited phagocytosis of yeasts with or without pretreatment with normal rabbit serum. Among the cells migrating from the explants, a population of round cells revealed properties of macrophages such as positive nonspecific esterase activity, surface receptors, and phagocytosis of coated erythrocytes. The results indicate that foam cells, which characterize the early atherosclerotic plaques of cholesterol-fed rabbits, possess structural and functional properties of macrophages. It seems likely that circulating monocytes are the prime source of foam cells in the early phase of atherogenesis.
Of 103 patients with membranous glomerulonephritis proved by renal biopsy, 11 (10.7%) had rheumatoid arthritis. Nine of these 11 patients received systemic treatment with anti-rheumatic remedies including gold, D-penicillamine and bucillamine. Two others were administered only token of nonsteroidal antiinflammatory drugs. Renal function of the patients was well maintained and within normal limits. Four patients showed nephrotic syndrome, while mild to moderate proteinuria was found in the other 7. Hematuria was minimal to mild, and it was not a major symptom. Six patients resolved proteinuria completely and 2 patients incompletely after discontinuation of chrysotherapy. Nine cases of the membranous lesion in patients with rheumatoid arthritis were stage 1. Thus it was often difficult to identify the glomerular change only by light microscopy. IgA nephropathy and AA amyloidosis were associated in one patient respectively. Our data lead us to conclude that chrysotherapy would cause membranous lesions, but rheumatoid arthritis itself also induce membranous glomerulonephritis.
The effects of hypercholesterolemia on both the initial and chronic phases of rat nephrotoxic serum (NTS) nephritis have been investigated. Injury during the initial phase of NTS nephritis in hypercholesterolemic rats maintained on a cholesterol-supplemented diet (Group 2) was characterized by segmentally accentuated accumulations of vacuolated cells with lipid droplets (foam cells) in the glomeruli, while the kidneys of rats fed a standard diet (Group 1) revealed only mild intracapillary cell proliferation. Immunoelectron microscopy showed that the foam cells observed in Group 2 rats were largely derived from macrophages. The glomerular macrophage number, defined by the number of ED1-positive cells per glomerulus, was significantly higher in Group 2 than in Group 1 animals at days 5–6 (3.4±1.4 in Group 1 against 6.3±1.0 in Group 2;p<0.01) as well as at days 21–28 (5.5±2.6 in Group 1 against 10.9±2.8 in Group 2;p<0.01). In contrast, the numbers of OX19-positive T-lymphocytes and OX33-positive B-lymphocytes were similar in both groups. In the chronic phase of NTS nephritis at week 20, semiquantitative evaluation of the glomerular lesions disclosed more severe focal segmental glomerulosclerosis (FSGS) in Group 2 compared with Group 1 animals (glomerular injury score: 14±10 in Group 1 against 73±17 in Group 2;p<0.01). Accumulations of lipid and foam cells were invariably seen in the sclerotic foci of Group 2 animals. The results indicate that hypercholesterolemia played an important role in the accelerated development of FSGS in rat NTS nephritis. The presence of lipid and the augmented influx of macrophages (foam cells) have close parallel with atherosclerosis and suggest that analogous pathogenetic mechanisms may be at work.
A submucosal tumor (SMT) was found during a regular health check-up in a 59-year-old man. Following barium meal study the SMT was shown to be growing. He visited our hospital for further examination.
Modern techniques of investigation have revealed several similarities between atherosclerosis and chronic inflammation, and that immune mechanisms seem to operate in the incipient and subsequent phases of atherosclerosis. In the present study, the fate and morphogenesis of human atherosclerosis was considered, and the immune aspects of atherogenesis were analysed, using fresh human aorta obtained from autopsy cases. One of the earliest changes in the grossly normal, lesion‐prone area of the aorta from young cases (prelesional changes) was the infiltration of blood‐borne T lymphocytes and monocytes/macrophages beneath the endothelium. Cell‐populated lesions abounding in T lymphocytes and rnacrophages, often bearing signs of activation, with or without cytoplasmic lipids were found in the fatty streaks, cap and shoulder regions of more advanced atheromatous plaques. The ultrastructural observation of cell‐rich areas suggested that cognate cell‐to‐cell interaction plays a pivotal role in atherosclerosis, as well as cytokine‐mediated paracrine or autorcrine mechanisms. From an immunological perspective, the areas where both cell types are especially numerous and in close proximity are considered to be the areas with an index of disease activeness or progressiveness. Also, the present authors show evidence of clonal expansion of T lymphocytes. It is most likely that the increase of intimal cells was caused by the recruitment of immunocompetent cells from the bloodstream into the intima and by the clonal expansion of T lymphocytes. In addition, dead or dying cells were identified in areas of different stages ranging from prelesional areas to atheromatous plaques. Thus, the initiation and progression of human atherosclerosis appears to be punctuated by brief episodes of immunological events related to cell infiltration, proliferation and death.
