Kinetics and regulation of granulocyte precursors during a granulopoietic stress

Studies were performed in splenectomized dogs to investigate the proliferative kinetics of the committed granulocyte-macrophage stem cells (CFU-c) and to evaluate the role of colony-stimulating factor (CSF) in the regulation of granulocytopoiesis. Eight to ten hours following intraperitoneal infusion of starch-saline, the peritoneal cavity was lavaged to remove leukocytes. Three successive lavages (I, II, and III) were done in each dog. The CFU-c concentration in the marrow cells of 4 dogs and in the blood cells of 2, obtained before, during, and after lavages, was assayed in soft-agar medium. The CSF activity of lavage fluids was measured by their ability to stimulate canine marrow cells to form granulocyte-macrophage colonies in soft-agar medium. Each lavage removed 14.6–17.5 × 10 9 cells (more than 75% segmented forms and less than 20% monocytes), and the neutrophils removed were equivalent to 97%-108% of their total blood granulocyte pool. Lavaging caused rapid entry of neutrophils from the marrow into the blood and increased granulocytopoiesis in the marrow from the time of lavage II, as reflected by an increased percentage of granulocytes in the multiplicative compartment. Decreases occurred in the percentage normoblasts in the marrow commencing from the time of lavage II and in absolute reticulocyte count in blood after completion of the lavages. Marrow CFU-c decreased to a minimum (30%-57% of control value in 3 of 4 studies) at lavage I or II. CFU-c recovery with overshoot occurred in 3 of 4 studies by the time of lavage III or a day later. The pattern of blood CFU-c changes was similar to that of the marrow. CSF in lavages I, II, and III was ~5, 2, and 1.8 times the control level, respectively. These results suggest that during an acute need for granulocytes the marrow CFU-c differentiate under the apparent influence of CSF to form granulocytes, and pluripotent hemopoietic stem cells differentiate along the granulocytic line with a concomitant reduction in the erythrocytic line.