Platelet-derived growth factor enhances granulopoiesis via bone marrow stromal cells

Platelet-derived growth factor (PDGF), a growth factor for connective tissu e cells, stimulates erythropoiesis and megakaryocytopoiesis in vitro but th e effect of PDGF on granulocyte proliferation remains unknown. The effect o f the recombinant human PDGF-BB isoform on granulopoiesis was investigated in this study. The results show that PDGF significantly stimulated murine c olony-forming unit-granulocyte-monocyte (CFU-GM) proliferation in a dose-de pendent manner (1 to 100 ng/mL) using murine bone marrow cells (n = 4). Max imum stimulation was obtained with 50 ng/mL of PDGF (P < .01). The effect o f PDGF on murine CFU-GM proliferation was compared with that of interleukin (IL)-3, IL-6, granulocyte monocyte colony-stimulating factor (GM-CSF), and acidic fibroblast growth factor (aFGF) at their optimal doses. The stimula ting activity of PDGF was higher than that of aFGF but lower than that of I L-3. IL-6, or GM-CSF There is no synergistic effect between PDGF and IL-3 o r IL-6, but a significant enhancing effect was observed in IL-3 plus IL-6. PDGF also stimulated the growth of CFU-GM with CFU-megakaryocyte in the pre sence of bone marrow stromal cells. We also found that PDGF had similar a e ffect on human CFU-GM proliferation using bone marrow mononuclear cells (MN C). However, the increase in PDGF-stimulated CFU-GM proliferation was inhib ited by anti-Gh I-CSF. anti-IL-3, and anti-IL-6 antibodies (n = 4), suggest ing that endogenously produced GM-CSF IL-3, and IL-6 may play a role in the PDGF-induced CFU-GM proliferation. Furthermore, PDGF (1 to 100 ng/mL) did not show any effect on CFU-GM proliferation when replacing bone marrow MNC with immunomagnetic selection-enriched CD34(+) cells from human cord blood (n = 5, purity, 91% <plus/minus> 6.5%). This study indicates that PDGF may indirectly enhance CFU-GM proliferation by inducing the bone marrow stromal cells to produce GM-CSF, IL-3, or IL-6, (C) 2001 The Japanese Society of H ematology.