Delineation of receptor-mediated colony-stimulating factor (CSF-1) utilization and cell production by precursors of mononuclear phagocytic series at various stages of differentiation.

Abstract

Colony-stimulating factor-1 (CSF-1) is a specific haematopoietic growth factor that stimulates the production of macrophages by both bone marrow macrophage precursors (GM-CFC) and certain more mature peripheral tissue macrophages. The relationship of CSF-1 utilization and cell production by macrophage precursors at various stages of differentiation was studied. Bone marrow GM-CFC had the highest proliferative capacity followed by blood monocytes and peritoneal exudate macrophages (PEM) as determined by their cell doubling time (DT) which was also dependent on the concentrations of exogenous CSF-1. PEM had the longest initial lag period before commencing cell proliferation. Exogenous CSF-1 was constantly utilized by the growing cells; depletion of available CSF-1 resulted in growth arrest and, subsequently, cell death. The production of macrophage progeny, per amount of CSF-1, correlated with parent macrophage maturity; for each 100 U of CSF-1 consumed, bone marrow precursor cells and blood monocytes were capable of producing 17.9 x 10(4) and 13.4 x 10(4) progeny, respectively, whereas PEM generated only 4.6 x 10(4) daughter cells. Thus, the removal and destruction of CSF-1 by more mature, less proliferative tissue macrophages may provide a possible mechanism by which CSF-1 levels are reduced and the production of early haemopoietic macrophage precursors controlled.