The molecular control of granulocytes and macrophages

The proliferation in vitro of granulocytes and macrophages can be regulated by the four colony stimulating factors (CSFs), stem cell factor and interleukin 6, with Flk ligand having a weaker action. Combinations of these glycoprotein regulators produce superadditive proliferative responses. The CSFs also influence commitment, maturation and mature cell functional activity and these various responses are initiated by distinct regions of the individual receptors. The injection of single CSFs into experimental animals or patients reproducibly enhances granulocyte or monocyte formation or function despite the existence of complex interacting networks of regulatory molecules. Verification of the importance of the CSFs for the regulation of basal haemopoiesis has been obtained by analysis of mice in which the genes encoding the CSFs or their receptors have been inactivated. In a casein-induced model of acute inflammatory responses, the migration of neutrophils from the marrow and localization of these cells to the inflammatory site appear not to be CSF-dependent processes even though major increases occur in CSF levels at the inflammatory site.