Long-term effect of heme oxygenase (HO)-1 induction in glomerular immune injury

In a rat model of macrophage-dependent glomerular immune injury induced by administration of antibody against the glomerular basement membrane (anti-GBM), the authors assessed the anti-proteinuric effect of Heme Oxygenase-1 (HO-1) induction. Rats received anti-GBM antibody alone, anti-GBM antibody and treatment with the HO-1 inducer, hemin, or non-immune serum (controls). Urine protein, creatinine, and nitrite/nitrate excretion were measured on days 5, 7, and 14 after administration of the anti-GBM antibody. In hemin-treated animals with anti-GBM antibody-induced immune injury, HO-1 immunolocalized in macrophages infiltrating glomeruli and in tubular epithelial cells. In these animals, proteinuria was decreased. There was also a decrease in blood urea nitrogen (BUN) levels without a change in serum creatinine or systemic blood pressure. The observations establish the anti-proteinuric effect of hemin induction. This effect could be mechanistically linked to blunting of the ability of infiltrating macrophages to cause injury or to changes in tubular handling of filtered protein.