Regulation of diffusion-chamber granulopoiesis by colony-stimulating factor

Studies were undertaken to examine the role of colony-stimulating factor (CSF) in controlling murine peritoneal diffusion-chamber (DC) granulopoiesis. Serum CSF was unchanged for 1-3 days after 700-750 rad total body irradiation. Variable increments were noted on the fourth and seventh days after irradiation. DC CSF increased four- to fivefold over serum activity within 24 h of implantation in control mice. An eight- to tenfold increment over serum levels was noted in DC CSF from irradiated mice. Both serum and DC CSF were neutralized completely by repeated injections of anti-CSF serum. DC granulopoiesis was studied by immobilizing marrow cells in plasma clots in peritoneal DC. Repetitive administration of anti-CSF serum or a purified monospecific anti-CSF antibody caused a marked reduction in DC granulopoiesis. This was characterized by a decrease in both the number and size of granulocyte colonies, with a 40%-80% decrease in total granulocytes per chamber. These findings indicate that the granulopoiesis observed in the DC of irradiated hosts is associated with an increase in local rather than systemic CSF production. Neutralization of the CSF reduces proliferation of the granulocyte progenitor cell and maturation of more differentiated granulocytic cells.