Erythropoietin production by macrophages in the regenerating liver

The site of erythropoietin (Ep) production and/or storage in the rat liver was determined. A guinea pig anti-Ep was produced against purified rat Ep (64,096 +/- 4j064 IU/mg). This antibody was found to be highly specific using rocket immunoelectrophoresis, Ouchterlony gel diffusion methods, and immunoprecipitin reactions as well as Ep neutralization tests (capable of completely neutralizing up to 2,000 IU Ep/mg). This anti-Ep was labeled with either fluorescein for light microscopic study or ferritin for electron microscopy. Kupffer cells showed varying degrees of labeling after hepatectomy alone or hepatectomy combined with nephrectomy and/or hypoxia. Greatest labeling was seen in Kupffer cells of rats that were nephrectomized 48 hr posthepatectomy and kept at ambient pressure. No labeling of hepatocytes or vascular and bile duct endothelium was noted.