Hepatic clearance of intact and desialylated erythropoietin.

BRIGGS, DANIEL W., JAMES W. FISHER, AND WILLIAM J. GEORGE. Hepatic clearance of intact and desialylated erythropoietin. Am. J. Physiol. 227(6) : 1385-l 388. 1974.-Following desialylation by neuraminidase, erythropoietin (ESF) is inactive in vivo but retains its activity when assayed in the in vitro bone marrow culture. This loss of erythropoietic activity in vivo has been attributed to a rapid clearance of desialylated ESF (dESF) from the circulation of the assay animal, although an increased rate of clearance of dESF has not been demonstrated. In this study, rat livers were perfused with diluted rat blood containing either ESF or dESF obtained from hypoxic rats. ESF or dESF content of the perfusates was determined by measuring the stimulation of 5gFe incorporation into heme in rabbit marrow cultures (in vitro). Perfusates containing dESF showed a rapid decline in erythropoietic activity after only 15 min of perfusion, whereas the activity of perfusates containing intact ESF remained elevated for several hours of perfusion. Desialylated, but not intact, orosomucoid prevented the loss of erythropoietic activity of dESF during liver perfusion. These results indicate that desialylation of ESF causes its rapid hepatic clearance from the circulation and that desialylated orosomucoid is able to competitively inhibit this process. These results also suggest that the mechanism of ESF catabolism by the liver is similar to that reported for certain other plasma glycoproteins.