In Vivo Effect of Interleukin - la on Hematopoiesis : Role of Colony - Stimulating Factor Receptor Modulation

To determine the mechanism(s) by which interleukin-I (IL-I) promotes granulopoiesis in vivo, we examined the effect of in vivo administration of IL-la on colony-stimulating factor (CSF) receptor expression on bone marrow cells (BMCs) and whether this directly correlated with progenitor cell responsiveness. Administration of IL-la to mice induced the upregulation of both granulocyte-macrophage-CSF (GM-CSF) and IL-3 receptors, which reached a maximum 24 hours after IL-la injection on unfractionated BMCs. This upregulation was more pronounced on the progenitor-enriched cell population (lineage-negative [Lin-1). The enhanced GM-CSF and IL-3 receptor expression directly correlated with enhanced IL-3or GM-CSF-induced growth of colony-forming unitculture (CFU-c) or CFU-mixture (CFU-Mix; colonies containing macrophages, granulocytes, and erythroid cells). In addition, the absolute number of high proliferative potentialcolony-forming cells (HPP-CFC) was increased fivefold. In