Cholesterol, macrophages, and gene expression of TGF-beta 1 and fibronectin during nephrosis.

Hypercholesterolemia aggravates experimental progressive glomerular injury. Evidence suggests the infiltrating glomerular macrophage (M phi) is a potential effector mechanism for the noxious effects of hypercholesterolemia. Because transforming growth factor (TGF)-beta 1 is secreted by activated M phi s and also stimulates fibronectin production by glomerular cells, we evaluated the kinetics of gene expression for these moieties in glomeruli isolated from nephrotic rats at 3, 7, 11, and 42 days after the delivery of puromycin aminonucleoside (PA).

Macrophages mediate adverse effects of cholesterol feeding in experimental nephrosis.

We tested whether the deleterious effects of hypercholesterolemia, in a progressive glomerular disease model, may be mediated by infiltrating renal macrophages. A single sublethal dose of whole body X-irradiation (XI) delivered to rats with acute puromycin aminonucleoside (PA) nephrosis fed a high-cholesterol (HC) diet resulted in significantly greater inulin and p-aminohippurate (PAH) clearances at 11 days after PA without any alterations in circulating lipid levels, in contrast to nonirradiated HC-fed nephrotic controls. This functional protection was associated with significant declines in both glomerular and cortical interstitial macrophage number.

Progressive albuminuria and glomerulosclerosis in a rat model of chronic renal allograft rejection.

A significant proportion of renal allografts fail within several months or years after transplantation, primarily because of chronic rejection. The etiology and pathophysiology of this condition remain unclear. We studied the renal function, morphology, and immunohistology, in parallel, among F344-to-Lewis allografts (n = 23) and isografts (n = 13) over the course of 24 weeks.

Sublethal X-irradiation during acute puromycin nephrosis prevents late renal injury: role of macrophages.

Acute puromycin aminonucleoside (PA) nephrosis is associated with a surge in the glomerular macrophage number. Whole body X-irradiation (XI) was used to assess whether bone marrow depression, which depletes normal rat glomeruli of macrophages, is efficacious in ameliorating progressive glomerular disease. A solitary, sublethal dose of XI (600 rad) was administered 3 days after PA delivery to rats (PA/XI) that were followed for 18 wk.