Characterization of an inhibitor of granulocyte/monocyte colony formation in leukemic chicken plasma.

The plasma of chicks with myeloblastic leukemia (induced by avian myeloblastosis virus, AMV) contained an inhibitor which blocked colony formation in vitro by marrow cells. It eluted in the second protein peak obtained by Sephadex G-200 gel filtration and was found in the diafiltrate following defiltration through a UM 10 membrane under acidic conditions. It was not extractable with chloroform, was heat-stable (65 degrees C, 30 min), pronase-sensitive and had a molecular weight less than or equal to 5000 daltons as determined by high performance liquid chromatography. Thus, it appears to be a small, acid-soluble, heat-stable peptide. It had no interferon activity. It was not present or present only at very low levels in normal plasma. Furthermore, it was not elevated in chicks infected only with the nonleukemogenic helper virus of AMV, and was, therefore, associated with leukemia rather than virus-replication. Leukemic myeloblasts, purified by passage in suspension culture, released the inhibitor. It acted directly on the colony-forming cell and inhibited normal cells much more than leukemic cells. In normal marrow, macrophage and granulocyte progenitors were affected. A similar inhibitor in normal plasma inhibited only granulocyte progenitors.