MATURE AND IMMATURE MYELOID CELLS DECREASE THE GRANULOCYTE-COLONY-STIMULATING FACTOR LEVEL BY ABSORPTION OF GRANULOCYTE-COLONY-STIMULATING FACTOR

We studied the effects of polymorphonuclear neutrophils (PMN) and imma ture myeloid cells on the granulocyte colony-stimulating factor (G-CSF ) level in vitro to better understand the regulatory mechanisms of neu tropoiesis. Intact normal PMN decreased the G-CSF level after incubati on with recombinant human (rh) G-CSF in a time-and dose-dependent mann er. The percent reduction decreased as the concentration of rhG-CSF in creased. However, the cell-free PMN-conditioned medium (PMN-CM) did no t decrease the G-CSF level. The intact PMN also decreased the granuloc yte-macrophage (GM)-CSF level after culture with rhGM-CSF, but did not affect the monocyte (M)-CSF level after culture with rhM-CSF. Normal bone marrow (BM) immature neutrophilic cells and G-CSF-dependent acute myeloid leukemic cells (OCI/AML la) also decreased the G-CSF level, w hereas K-562 cells, which have no detectable G-CSF receptors, did not affect it. Phenylarsine oxide (PhAsO), an inhibitor of endocytosis of ligand receptor complex, abrogated this decreasing effect of intact PM N and OCI/AML la cells. These findings suggest that mature and immatur e myeloid cells negatively regulate neutropoiesis by, at least in part , decreasing the G-CSF level probably through receptor-mediated contin ual absorption and metabolism of G-CSF. (C) 1998 Elsevier Science Irel and Ltd. All rights reserved.