Granulocytopoiesis. II. Emergence and Pattern of Labeling of Neutrophilic Granulocytes in Humans

Abstract 1. Following administration of H3-thymidine to 15 patients with a variety of hemopoietic conditions, the emergence and the pattern of labeling of neutrophilic granulocytes were studied in peripheral blood leukocytic concentrates. The hematologic diagnosis included five in which the hemopoiesis appeared to be in a steady state equilibrium at the time of study, three with various types of leukemia, one with lymphosarcoma, two with multiple myeloma, one with myelofibrosis, two with pernicious anemia (once before and once after therapy) and two with bacterial infections. 2. The emergence time of neutrophilic segmented granulocytes (time from H3-thymidine injection to the first appearance of labeled segmented forms in the peripheral blood) was found to vary in steady state equilibrium from 96 to 144 hours. It was shortened to 48 hours in two instances with bacterial infection. This was interpreted as indicating a faster than normal nuclear maturation with normal or delayed cytoplasmic maturation (dissociation in nuclear and cytoplasmic maturation). 3. The number of segments of neutrophilic granulocytes was found to be unrelated to cell age as had been hypothesized by Arneth many years ago. However, bandforms were found in the circulation about 24 hours earlier than segmented forms, suggesting that they are younger and that some are acceptable to the blood while others continue to mature to segmented forms. Pelgeroid cells with round or bilobed nuclei found in one case of subleukemic myelocytic leukemia were found to emerge simultaneously 132 hours after H3-thymidine injection. This suggests that both types are identical in their degree of maturation. Thus the cells with round nuclei are not band forms but result possibly from a delayed nuclear maturation. 4. In patients studied for at least 2 weeks, characteristic undulations of the labeling indices of the segmented granulocytes were found. If the sampling intervals were 24 hours, peaks were found 6 days apart, the second peak being about half of the labeling index of the first. If the sample interval was shorter, a finer structure was observed with undulations showing peak intervals of 2-3 days. Although the significance is obscure at present, the constancy of the findings suggest that there may be a constant input of cells with the index of labeling varying due to some synchrony of the precursor population(s). Alternative explanations are discussed.