Human early and late granulocyte-monocyte progenitors (granulocyte-macrophage colony-forming units, CFU-GM), depleted of accessory cells, were physically separated using an antimyeloid monoclonal antibody (DS1.1). They were separately cultured at optimal growth conditions and tested for responsiveness to prostaglandin E2 (PGE2), recombinant tumor necrosis factor alpha (TNFα), and transforming growth factor beta-1 (TGFβ1). Late (DS1.1+) CFU-GM displayed the highest sensitivity to PGE2 and TNFα, the first significant inhibition being evident at 10-9M PGE2 and 1 U/ml TNFα. Conversely, their growth was stimulated (211%-217%) by 0.25-2.5 ng/ml TGFβ1. Early (DS1.1-) marrow CFU-GM evidenced a lower sensitivity to PGE2 and TNFα. Their growth, however, was inhibited by 0.25-2.5 ng/ml TGFβ1. Early CFU-GM constitute the totality of peripheral blood myeloid progenitors. Cord blood CFU-GM were also demonstrated here to be entirely DS1.1-. Both adult and cord blood CFU-GM displayed the highest resistance to PGE2 and TNFα. By contrast, they showed the maximum sensitivity to growth inhibition by TGFβ1, active at 0.025-0.25 ng/ml. For the first time, therefore, highly purified subsets of human CFU-GM were separated that displayed a different responsiveness to well-defined growth-regulatory molecules. Our results indicate that TGFβ1 has a dual activity; it is inhibitory on early and stimulatory on late CFU-GM, whereas PGE2 and TNFα preferentially inhibit late CFU-GM growth.
|Number of pages||6|
|Publication status||Published - 1991|
ASJC Scopus subject areas
- Cancer Research
- Cell Biology