Chemical mediators of granulopoiesis: A review

Advances in the culture of primitive hemopoietic cells have added to our understanding of granulopoiesis. Granulocyte production appears to be under both stimulatory and inhibitory control. Colony stimulating factor (CSF), a group of glycoproteins, are specific stimulants of granulocyte and monocyte progenitor cells (CFU(C)) and may be analogous to erythropoietin. CSF differ in several respects from erythropoietin, however. CSF is elaborated by endothelial cells, monocytes, and macrophages which have intramedullary as well as extramedullary distributions in contrast to erythropoietin which is elaborated chiefly by the kidney. Second, CSF may hot have wide cross-reactivity amongst various species, and may comprise subsets with activity for neutrophil, monocyte, and eosinophilic progenitors. The inhibitory control of granulopoiesis is less well established than the stimulatory. The most promising candidate for a negative feedback mediatory is colony inhibiting activity (CIA), a glycoprotein similar to, if not identical with, lactoferrin. CIA, like lactoferrin, is elaborated by polymorphonuclear neutrophils. This molecule appears to act by reducing colony stimulating factor production by monocytes. Prostaglandins of the E-type and other low molecular weight inhibitors of granulopoiesis have suggested that negative feedback control of granulopoiesis is achieved by the ingestion and killing of invading microbes, thereby reducing the stimulus to CSF production by monocytes and other cells. At present, there is no decisive evidence that CSF or other granulocyte modulating substances in vitro are in vivo regulators. Purification of stimulatory and inhibitory molecules and the development of sensitive assays for them in human tissue fluids will be required to permit an assessment of their in vivo significance.