Inhibition of myeloid differentiation by mature granulocytes can be reversed by humoral factors.

Human mature granulocytes added to in vivo diffusion chamber (DC) cultures of murine bone marrow cells (BMC) led to a late reduction of CFU-C, day 5, and proliferative granulocytes, day 6. Cell free DC fluid harvested on day 4 from chambers with BMC and mature granulocytes slightly reduced granulocyte formation in new DC cultures, but not more than DC fluid from control cultures (BMC). Mice which had carried chambers of either group for 4 d, were not different when used as hosts for new DC cultures. However, they were less able to stimulate cell growth in DC than untreated mice. Tranfer of DC to new host mice on day 2 completely reversed the inhibition by mature granulocytes which otherwise could be detected in numbers of CFU-C on day 5 and proliferative granulocytes on day 7. However, CFU-S numbers were reduced on day 5 following reimplantation indicating an increased differentiation of CFU-S. Transfer of DC as late as day 4, rapidly restored the granulocyte numbers in the granulocyte co-culture group suggesting that also more differentiated granulocytes were stimulated to further growth and differentiation. It is proposed that factors from mature granulocytes reversibly inhibit myeloid differentiation. Differentiation can again be induced by factors which reach the DC shortly after intraperitoneal implantation in a mouse.