Evaluation of marrow granulocytic reserves in normal and disease states.

1. In the normal steady state granulocytopoiesis is confined to the marrow. There is general agreement that cell division in the granulocytic series does not occur after the myelocyte stage. 2. In the normal liuiiiaii in the steady state the granulocyte remains in the marrow for a I)eriOd of several days, probal)hy five to six days, after the last division of granulocyte precursors. After maturation occurs, the majority of granulocytes are released into the l)lOOd in an orderly fashion. This maSS of granulocytic cells ( which we have called the marrow granulocyte reserve, or NIGR, and which is incapable of proliferation ) comprises 1l)Out five-sixths of the marrow granulocytic cell population. It is evident that this intran edullary mass of maturing cells is iuaiiy tin es larger than the circulating mass of granulocytcs. This was sho vn in leukopheresis experiments in normal and heavily irradiated dogs.’3 Yoffey estimates th ratio of uiarrow to blood granulocytes at about one hiuiulred to One in the guinea pig.’ Recently, Donohue et al.5 have estimated a ratio of 25 to 30 to 1 in the human, em )loying an ingenious method for quantitating the marrow crythroid elements with Fe ”. Osgood arrive(l at a comparable relationship on the basis of his calculations.” 3. The rise in circulating granulocyte l4ulnber in rcspon e to such stimuli a leukopheresis or the intravenous injection of bacterial endotoxin is due to the accelerated entry of granulocytes into the blood from the marrow granulocyte reserve.:i,T This was established by labeling granulocyte desoxyribose nucleic acid (l)NA) and taking advantage of the time interval when the marrow granulocyte population was highly labeled relative to the circulating cells. Induction of a demand for increased granulocytes in the periphery at a time when the MGR is completely labeled will cause an acceleration in the rise in circulating granulocyte l)NA Pa2 specific activity. Accordingly, the majority of cells contributing to the peripheral demand came from the highly labeled marrow population and not from the unlabeled cells in various peripheral organs. 4. In the normal steady state, granulocytes which enter the peripheral blood from the