The response of murine splenic granulocyte-macrophage colony-forming cells to lipid A in vivo.

The physical and biological properties of murine splenic granulocyte-macrophage colony-forming cells (GM-CFC) were analyzed after the injection of the splenic hemopoiesis stimulating agent lipid A. In continuous gradients of Percoll, the majority of the splenic GM-CFC of untreated mice peaked at a buoyant density of 1.090 g/cm3, while a small second GM-CFC peak could be detected at 1.065 g/cm3. One day after the injection of lipid A, the splenic GM-CFC were almost equally distributed among these two density peaks. This altered proportion was still detectable 72 to 96 h later, although to a smaller extent. No difference in the responsiveness to the colony-stimulating factor (GM-CSF) from mouse-lung conditioned medium (MLCM) was observed between these two density subpopulations. The differentiation pattern of splenic GM-CFC was altered after the injection of lipid A. However, this altered pattern was the same in both density subpopulations. The percentage of splenic GM-CFC as well as the percentage of multipotent hemopoietic stem cells (CFUs) in DNA synthesis were markedly elevated after the injection of lipid A. A striking difference in the proliferative activity was found between high- and low-density GM-CFC in post-lipid A spleens. 24 h after the injection of lipid A, 43% of the high-density GM-CFC subpopulation was found in S according to the suicide technique using tritiated thymidine, whereas in the low-density fraction only 10% of the population was killed. This finding allows alternative interpretations.