Prostaglandin-E-mediated modulation of human marrow CFU-GM Ia-antigen expression: kinetics and specificity

In suspension culture, human granulocyte-macrophage colony-forming cells CFU-GM lose the ability to express Ia antigen within 3-6 h and coincidently become insensitive to inhibition by prostaglandin E (PGE) and acidic isoferritins (AIF). However, when cultured in the presence of PGE, Ia+ CFU-GM sensitive to inhibition by these regulatory factors can be detected after 24 h. Kinetic analysis indicates that the effects of PGE on CFU-GM Ia-antigen expression and growth response detected after 24 h in culture are (a) initiated within the first 3 h in suspension phase, (b) are essentially irreversible under the culture conditions employed, and (c) persist for up to seven days provided PGE is added at culture initiation. The demonstrated capacity of PGE to modulate day-7 CFU-GM Ia antigen and consequently responsiveness to inhibition extends also to day 14 CFU-GM. The effects of PGE on progenitor cell Ia-antigen expression appear specific for prostaglandins of the E series (PGE1, PGE2) and do not appear to be mediated via cyclic AMP. These studies provide additional evidence for a direct regulatory association between Ia antigens and control of hemopoietic cell proliferation, and support and further define a new role for PGE in the positive regulation of myeloid cell differentiation.