AJP - Renal Physiology, Vol 260, Issue 6 779-F786, Copyright © 1991 by American Physiological Society
Sublethal X-irradiation during acute puromycin nephrosis prevents late renal injury: role of macrophages
J. R. Diamond and I. Pesek-Diamond
Division of Nephrology, Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033.
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. In contrast to a sham-irradiated nephrotic cohort (PA/Sham), the
PA/XI rats had a complete prevention of the recurrent albuminuria and
manifested a significant reduction in the percent of glomeruli exhibiting
glomerulosclerosis (GS) lesions at 18 wk after PA. XI significantly reduced
the glomerular and interstitial macrophage number as well as the
circulating white blood and monocyte counts during peak albuminuria. This
protection was independent of the magnitude of the acute albuminuria and
elevations in the circulating lipid levels. These data show that whole body
XI delivered during acute nephrosis is capable of preventing progressive
glomerular disease in association with a reduction in the glomerular and
interstitial macrophage number. Additionally, this study suggests that this
immune effector cell is important in mediating the propagation of initial
glomerular injury to GS.
