Inhibition of CFU-E in rat bone marrow perfused with 2'-5'-oligoadenylate core

Several 2'-5' oligoadenylate (2-5A) core molecules were tested for their inhibitory effect on erythroid colony-forming units (CFU-E). These compounds were introduced into the CFU-E microenvironment by vascular perfusion of isolated rat hind limbs. The marrow microvasculature did not appear to be damaged by these procedures when examined by electron microscopy. After a brief in situ exposure to 2-5A core, the marrow cells were grown in methylcellulose medium with added erythropoietin (Ep). Maximum percent inhibition of CFU-E was obtained with 2-5A trimer core. The tetramer core was less effective, and no inhibition of colony formation was seen in cultures of marrow perfused with 2-5A dimer core. From this it was concluded that the inhibitory effect of 2-5A trimer core was highly specific. Furthermore, this effect was of long duration, since when 2-5A trimer core was given just prior to Ep the CFU-E were blocked in their differentiative response to Ep for 48-72 h.