Phagocytosing neutrophils rapidly release a factor which inhibits granulopoiesis in vitro

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.