When granulocytes are labeled with diisopropylfluorophosphate (DFP32) and then returned to the circulation of the donor, the labeled granulocytes are distributed in a pool of cells which is approximately two times larger than that calculated from the blood volume and the concentration of granulocytes in the circulating venous blood (1, 2).This pool has been referred to as the total blood granulocyte pool (TBGP) and it consists of two subcompartments or pools. These pools have been designated the circulating granulocyte pool (CGP) and the marginal granulocyte pool (MGP). The size of the CGP can be calculated from the blood volume and the absolute granulocyte count. Equilibration between the granulocytes in the CGP and in the "noncirculating" or MGP is sufficiently rapid and complete to allow these two pools to be considered as one kinetically, and the size of the TBGP can be determined by the isotope dilution principle. Since the cells are removed from the TBGP in an exponential fashion with a mean half-time disappearance (Ti) of 6.6 hours, the granulocyte turnover rate (GTR), that is, the number of granulocytes turned over through the blood in a unit of time, can be calculated.The purpose of this paper is to present data on the GTR in normal subjects, as well as additional data on the size of the TBGP, CGP and MGP in normal subjects. The influence of steroids, physical exercise, epinephrine and bacterial endotoxin on these parameters in normal subjects has also been studied.

In a previous publication (1) it was noted that when granulocytes were labeled in vitro with radioactive diisopropylfluorophosphate (DFP32 ) and then returned to the circulation of the donor, about half of the labeled cells could not be found in the circulation at the completion of the infusion (T0). Thereafter the remaining labeled cells left the circulation in a random fashion with a mean halftime disappearance (T.) of 6.6 hours.Since cell damage and significant elution of the label could not be demonstrated tinder the conditions of the study, it was suggested that the immediate disappearance of half the infused cells was due to their rapid dilution in a larger pool than that calculated from the blood volume and the venous granulocyte count.The concept that the circulating granulocyte pool (CGP) does not constitute all of the intravascular leukocytes is not new. Vejlenis (2)

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Although it seems evident that the neutrophilic leukocytosis commonly encountered in patients with purulent infections, polycythemia rubra vera, and a variety of other clinical disorders probably indicates an increased mass of neutrophils in the blood and increased neutrophil production, turnover, and utilization, it has not been possible to quantify these processes directly until recently. In normal subjects it was demonstrated that approximately one-half of the neutrophilic granulocytes in the blood are circulating freely [circulating granulocyte pool (CGP)], whereas the remainder adhere to the walls of small venules [marginal granulocyte pool (MGP)] (1). Since these two pools were shown to be in rapid equilibrium with each other they may be considered to form a single total blood granulocyte pool (TBGP) for kinetic purposes. These facts together with the finding that neutrophilic granulocytes disappear from the blood in a random manner (2) have made it possible to approximate the rate of production and destruction of neutrophils in normal man.In the present study the size of the TBGP, the distribution of cells in the two subcompartments, the CGP and the MGP, the blood granulocyte half disappearance time (tj), and the granulocyte turnover rate (GTR) were measured in patients with polycythemia vera, myelofibrosis, chronic infections, and diseases of other kinds. Studies in patients with chronic myelocytic leukemia are the

1. A method, based on the uptake of radioiron into heme, is described for the measurement of heme synthesis in a hemolysate of chicken erythrocytes. 2. The addition of glycine, δ-aminolevulinic acid, porphobilinogen or protoporphyrin 9 to the system augmented heme synthesis. 3. Citrate potentiated heme synthesis in the presence of glycine, but had no effect when porphobilinogen was added. Succinate, in the presence of glycine did not enhance heme synthesis. 4. The addition of coproporphyrin I or III, or uroporphyrin I or III, did not augnment the uptake of radioiron into heme. The addition of mesoporphyrin 9 or hematoporphyrin 9 enhanced the uptake of radioiron. These studies are iterpreted as suggesting that protoporphyrin, but not uroporphyrin or coproporphyrin, is a precursor of heme. For reasons discussed, further work will be necessary to determine if mesoporphyrin and hematoporphyrin are precursors of protoheme. 5. The synthesis of heme was inhibited by the addition of malonate or lead. Evidence is presented that both of these substances affected heme synthesis at several different levels, particularly the formation of δ-aminolevulinic acid and the incorporation of iron into protoporphyrin. 6. Plasma extracts from chickens, made anemic by bleeding or by the administration of phenylhydrazine, did not potentiate heme synthesis. 7. Normal, nonreticulated, human erythrocytes failed to synthesize heme in the presence of glycine, δ-aminolevulinic acid, porphobilinogen on protoporphyrin 9.