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Sequestration and degradation of red blood cells (RBC) are believed to occur in part in the liver, but the magnitude and cellular localization of this process remain uncertain. This problem was studied in rats by investigating isolated parenehymal and sinusoidal cell populations of the liver. After digesting the perfused liver with pronase, hepatic sinusoidal cells were isolated free of RBC and debris. Of the isolated cells, 90 % were phagocytic, as judged by their uptake of colloidal ~gSAu or of aggregated albumin-lalI administered in vivo After administration of spherocytic (heat-treated) RBC, however, only about one quarter of the isolated cells were found to contain phagocytized RBC. This apparently distinct popula~ tion of RBC-phagocydzing cells is designated as '°erythrophagocytic (EP)" ceils. The EP cell population was further characterized functionally by its specific phagocytosis of coltoidaI carbon and of 99mtechnetium-sulfur colloid and histochemically by its peroxidase activity. The role of the EP population in the catabolism of RBC-hemoglobin was studied in isolated hepatic sinusoidal ceils by assay of microsomal heme oxygenase (MHO), which is the inducible enzyme system that converts heine to bilirubin. The MHO activity of individual sinusoidal isolates was related directly to their content of EP ceils

The liver participates in the removal from the circulation of both damaged red blood cells (RBC) and plasma hemoglobin. The specific hepatic cell types involved in these processes have been identified by fractionation of rat liver into pure isolates of parenchymal and sinusoidal cells. After injection of 59Fe-labeled hemoglobin, 85%-95% of the radioactivity in the liver was associated with the parenchymal cells, regardless of whether the hemoglobin was bound to haptoglobin or was free in plasma. By contrast, 59Fe-labeled spherocytic RBC were sequestered entirely by the sinusoidal cell population. Stimulation of microsomal heme oxygenase by administered hemoglobin or RBC indicated that these cell fractions not only sequester but also degrade the ingested hemoglobin-heme. Infusion of doubly labeled 59Fe, 125-I-hemoglobin indicated that the hepatic parenchymal cells remove the intact hemoglobin molecule without exchange or transfer of the heme moiety to other carrier proteins. By contrast, heme bound to albumin was detached from the albumin before its uptake by the parenchymal cells. These findings suggest that, contrary to previous belief, hepatic parenchymal cells play a key role in the metabolism of plasma hemoglobin.

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