Hemoglobin and Erythrocyte Catabolism in Rat Liver: The Separate Roles of Parenchymal and Sinusoidal Cells

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.