The number of granulocytic progenitor cells (colony forming units in culture: CFUc) in the blood of patients with Down's syndrome was found to be reduced by 73.2% when compared to a group of age and sex matched controls. However, the blood CFUc of the Down's syndrome patients and the controls showed similar sensitivity to hydroxyurea which suggests that the low number of progenitor cells in Down's syndrome is not compensated by a marked increase in their cellular proliferation. The colony size distributions were similar for both the patients and the controls and, in addition, repeated assays at various intervals revealed no marked fluctuation in the number of blood CFUc in either group. The significance of the reduced number of circulating CFUc in Down's syndrome in relation to the known susceptibility of such patients to leukaemia is discussed.

Marked changes in the concentration and proliferative state of circulating granulocytic progenitor cells (colony forming units in culture; CFUc) were observed in female patients following surgical trauma. Within one day of an abdominal hysterectomy there was an abrupt fall in the number of blood CFUc to between 10% and 20% of normal and an increase in the proportion synthesizing DNA which coincided with the maximum neutrophilia. Subsequently, as the neutrophil count declined, the CFUc concentration increased to supranormal values and the proliferative response persisted, both parameters returning to normal 2 weeks after surgery. These results suggest that, following surgical trauma, the increased demand for neutrophils is rapidly met by increased CFUc proliferation.

A double layer agar technique was used to investigate the proliferative state of granulocytic progenitor cells (Colony Forming Units in Culture; CFUc) in human peripheral blood and bone marrow. The sensitivity of the progenitor cells to the S‐phase specific agent, hydroxyurea, was used as an index of the proportion of cells engaged in DNA synthesis. In the presence of low concentrations of colony stimulating factor (CSF) the CFUc were found to be virtually insensitive to the drug. However, when cultured in the presence of increasing concentrations of CSF the proportion of CFUc apparently killed by hydroxyurea increased to a maximum of 23% for those cells in the blood and 39% for those in the marrow. The results indicate that CFUc which are slowly proliferating are sensitive to low concentrations of CSF. In contrast, those CFUc which are proliferating more rapidly require high concentrations of CSF before they will form colonies in culture. A model has been devised which suggests that as CFUc mature, their cell cycle time shortens and their sensitivity to CSF decreases.

Phagocytosis of the heat-killed opsonised yeast, Candida guilliermondii, by human neutrophils resulted in the rapid release of a potent factor which suppressed granulopoiesis in vitro. The factor has been shown to act on monocytes and macrophages by inhibiting the production and release of colony-stimulating factor (CSF) which is the specific stimulator of granulocytic colony-forming cell (CFUc) proliferation in vitro. When added directly to target cells containing CFUc, the inhibitory factor had no effect on colony growth. The absence of detectable inhibitor in media conditioned for short periods with resting neutrophils or neutrophils challenged with unopsonised Candida which are not phagocytosed confirmed that active phagocytosis was the stimulus for inhibitor release. In further experiments, addition of endotoxin to the cultures was shown to suppress the inhibitory effect. We suggest that feedback inhibition of CSF production in vivo may be mediated by products derived from phagocytosing neutrophils.