Erythropoiesis Inhibiting Factor(s) in Intact and Haemolyzed Red Blood Cells

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Abstract
A previous report have shown that both intact red blood cells (RBC) and an equal number of haemolyzed cells were able to inhibit erythropoiesis on ESF-induced erythropoiesis, suggesting a cell compound to be responsible for the inhibitiory effect. Haeme and haeme compounds have been found to stimulate or inhibit both erythropoiesis and haeme synthesis. The present work presents data on the inhibitory effect of haemolyzed RBC and compounds from intact RBC on erythropoiesis. The inhibiting factor was found to be of a small molecular size and of the same range as a urinary erythorpoiesis inhibiting factor (EIF). The inhibitor did not contain haeme. Both Fe+2 and Fe+3 were tested, showing no reduction of the 59-Fe incorporation into RBC in the test animals. The inhibition could not be due to dilution of the 59-Fe with unlabelled iron from the haemolyzed cells. On the contrary, Fe+3-ions rather stimulated erythropoiesis, probably due to increased amounts of available iron. Haemolysates were prepared from RBC with different amounts of immature cells. With increasing amounts of reticulocytes, a reduction of the inhibitory effect occurred. Also foetal cells showed less inhibition than an equal amount of adult cells. After high speed centrifugation, the inhibitory effect of haemolysates was found in the supernatant, while ghost cells exerted no inhibition. No species differences were found using both exhypoxic polycythaemic mice and rats. An inhibiting factor was liberated into the incubation medium when RBC were incubated for 20 h. No haemolysis occurred during the incubation period. Mature, adult RBC therefore contain a substance which is different from haeme, with a negative feedback on erythropoiesis.