Analytical review of structure and regulation of hemopoiesis.

Historical aspects of the accumulation of knowledge on the structure and kinetics of hemopoiesis are considered. Particular emphasis is placed upon kinetics of granulopoiesis based upon labeling of human granulocyte progenitors by tritiated thymidine (3HTdR) and the flow of labeled cells through mitosis and from a terminal mitosis through the non-dividing granulocytic pool into the blood. DNA synthesis time in myelocytes is 12-14 hours. The time from labeling of the myelocyte by 3HTdR to the appearance of labeled granulocytes in the blood is about 100 hours. Lobar pneumonia reduced the transit time from 100 to 48 hours in one patient. The deterministic model for granulopoiesis in human beings is described. Sterile inflammation and its effects on granulopoiesis was studied in the dog. Inflammation in tissue far from the bone marrow resulted in: 1. recruitment of a larger fraction of myelocytes into DNA synthesis; 2. increase in the rate of DNA synthesis in myelocytes; 3. increase in the number of mitoses in myelocytes; 4. increase in the rate of messenger transcription and translation so that a process involving synthesis of dozens of enzymes with their packaging into granules is shortened from 40 to 8 hours. It is likely that intramedullary production of GM-CSF and G-CSF are involved in the above processes. The nature of the chemical signal that mobilizes stored granulocytes from the marrow is not clear. Is there a factor produced in the inflammatory zone which circulates to the marrow and stimulates intramedullary production of GM-CSF and G-CSF? If so, are these the sole molecular regulators responsible for increasing the rate of granulopoiesis upon demand?