Renal Impairment and Intraglomerular Mononuclear Phagocytes in Cholesterol-Fed Rabbits

Abstract

Morphological and immunohistochemical studies using the anti-macrophage monoclonal antibody RbM2 were performed in cholesterol-fed rabbits. From the beginning of the experiment, the levels of lipoproteins showed the pattern of familial type III hyperlipoproteinemia patients, and glomerular endothelial and mesangial cells had lipid deposits. By the 3rd week, RbM2-positive cells appeared in the capillary lumina. These cells became larger and increased in number after the 8th week. Although they had become very large and had increased noticeably by the 20th week, few sclerotic glomeruli were observed. We could hardly detect any proliferation of or foamy changes in the mesangial cells, and monocyte/macrophages showed no proliferative capacity within the glomeruli. These findings suggest that hyperlipidemia alone did not cause proliferation or foam transformation of the mesangial cells. The glomerular macrophages, probably derived from circulating monocytes, did not induce a glomerular injury under the short-term hyperlipidemic conditions of these experiments.

Glomerulosclerosis in Adriamycin-induced nephrosis is accelerated by a lipid-rich diet

“…This was further supported by the fact that serum from animals with alimentary hyperlipidemia has a stimulating effect on cell proliferation [7], and low-density lipoprotein (LDL), a major lipoprotein elevated in nephrotic hyperlipidemia, has been found to be a growth factor for mesangial cells [16]. Alternatively, it is also possible that the mesangial hypercellularity results from infiltrating monocytes/macrophages into mesangium [5,7,12]. It is believed that glomerular foam cells derive from monocyte/macrophages in the animal hyperlipidemia model of glomerular injury [17,18].…”

“…Subsequently, much evidence has suggested that lipids are involved in renal injury. Diet-induced hypercholesterolemia has been shown to cause renal injury in rats, rabbits and guinea pigs [5,11,12]. However, this form of lipid-induced glomerular injury is relatively modest [4,12].…”

“…Diet-induced hypercholesterolemia has been shown to cause renal injury in rats, rabbits and guinea pigs [5,11,12]. However, this form of lipid-induced glomerular injury is relatively modest [4,12]. Recently, several investigations have suggested that the development of glomerulosclerosis requires not only hyperlipidemia, but also other forms of glomerular injury.…”

Hyperlipidemia aggravates renal disease in B6.ROP Os/+ mice

“…The extent to which hyperlipidemia might contribute to such chronic renal injury as diabetes or nephrosclerosis is not yet clear. The situation is different in experimental settings where hyperlipidemia has been demonstrated to induce renal injury in a variety of animal models such as dietary induced hyperlipidemia in rat [28][29][30], guinea pig [31], and rabbit [32], as well as in genetic hyperlipidemia in the obese Zucker rat [33] and the apolipoprotein E −/− mouse [34]. In this study we examined the effect of hyperlipidemia in mice with reduced nephron mass, a situation common in humans as a result of aging, remote glomerulonephritis, vascular disease, or nephrectomy.…”

A novel method to quantify the turnover and release of monocytes from the bone marrow using the thymidine analog 5′-bromo-2′-deoxyuridine

“…The thymidine analog 5Ј-bromo-2Ј-deoxyuridine (BrdU) was used to label dividing monocytes in the bone marrow and follow their release into the circulation. The monocytes that were labeled with BrdU in the marrow were specifically identified as monocytes in the peripheral blood using the monoclonal antibody RbM2 that is specific for rabbit monocyte lysosomal antigen (23,26,44). The kinetics of these cells was examined both in the normal control state and in a well-established model of pneumococcal pneumonia in rabbits (33).…”