Combined effect of friend polycythemia virus and erythropoietin on erythroid burst formation in vitro.

The infection of mouse bone marrow or spleen cells in vitro with the polycythemia strain of Friend virus (FVP) results in the formation of erythroid bursts after 4-6 days in plasma clot or methylcellulose cultures in the absence of added erythropoietin (Ep). We have now used this cell culture system to study the effect of added Ep on FVP-induced burst formation. The number of bursts that developed following infection of bone marrow cells with equilibrium density gradient purified FVP was increased by the addition of low concentrations of highly purified human urinary Ep (70,000 units/mg protein) to the infected cultures. The addition of as little as 0.001 unit per ml of Ep to infected cultures resulted in a 2-fold increase in burst formation. Increasing the concentration of Ep to 0.05 unit per ml caused a 4-fold increase in the number of bursts that developed. These concentrations of Ep were ineffective in inducing erythroid bursts when added to cultures of uninfected cells. The addition of Ep within 6 hr after FVP infection was necessary to observe increased burst formation. These experiments demonstrate that FVP-burst formation is enhanced by extremely low levels of Ep. Although a precise mechanism for the increase in FVP-induced erythroid bursts with added Ep is not apparent from these experiments, a number of possibilities are discussed.