Regulation of bone marrow cell growth in diffusion chambers: the effect of adding normal and leukemic (CML) polymorphonuclear granulocytes.

Inhibition of granulopoiesis was studied using the diffusion chamber (DC) technique. When mature granulocytes from human blood or syngeneic mouse peritoneal fluid were added to mouse bone marrow cells cultured in DC, a significant depression of granulopoiesis took place, and a stimulation of macrophage formation was observed in 7-day cultures. Human granulocytes had a stronger inhinitory capacity than mouse granulocytes. The inhibition appeared to be tissue-specific and caused by a diffusible factor. A time study showed that the added granulocytes had no observable effect on the growth of proliferative granulocytes and CFU-C during the first days of culture. A rapid decrease of proliferative granulocytes after day 5 was preceded by a similar reduction of CFU-C 1 day earlier. The effect of CFU-S was more variable. In one strain of mice, there was a consistent increase in the granulocyte co-culture group, whereas in another strain a significant increase was observed only on day 2. Hislotologic examination showed that mature granulocytes changed the colony distribution, so that a significant relative decrease of granuloid colonies occurred. The nature of this delayed suppression of granulopoiesis is not evident from these data. A possible explanation is that factors released by mature granulocytes prevent recruitment of CFU-C and granulocyte precursors from the CFU-S compartment by blocking the granulopoietic pathway. Leukemic (CML) granulocytes isolated from blood were less able to inhibit granulopoiesis than normal granulocytes with mouse bone marrow as well as human bone marrow as target cells.