Placental growth factor attenuates suppression of erythroid colony formation by interferon.
Placental growth factor (PlGF) is a member of the vascular endothelial growth factor family and is associated with inflammation and with pathologic angiogenesis. PlGF is released from marrow erythroid cells, and serum PlGF concentrations have been reported to distinguish sickle cell patients from healthy controls. We observed that erythroid colony forming units (CFU-Es) from homozygous sickle cell (SS) patients are less sensitive to inhibition by rhgammaIFN than those from healthy controls, and the contribution of PlGF to this process was evaluated. At 10-1000-pg/mL concentrations, PlGF neither inhibits nor enhances CFU-E colony formation, and no differences were observed between the responses of SS patients or healthy controls. rhPlGF 100 pg/mL reversed the inhibitory effects of rhgammaIFN on CFU-E colony formation. rhPlGF significantly attenuated rhgammaIFN induction of the Fas ligand in an erythroid cell line (HCD57). Both HCD57 cells and CD36+ human marrow cells express Flt-1, which is a receptor for PlGF. A neutralizing antibody against Flt-1 partially attenuated the IFN-protective effect of rhPlGF, although this effect was not statistically significant. In conclusion, increased PlGF concentrations in the marrow of SS patients may protect erythroid progenitors from cytokine-induced inhibition of colony formation, and it may be a mechanism by which erythropoiesis in sickle cell disease is preserved despite concurrent inflammation.
Dallalio
Gail
G
Medical and Research Services, Lexington Department of Veterans Affairs Medical Center, USA.
Means
Robert T
RT
D000755:Anemia, Sickle Cell / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D000906:Antibodies / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004347:Drug Interactions; D041905:Erythroid Cells / Q000166:cytology* / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects / Q000276:immunology; D053222:Fas Ligand Protein / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D017978:Receptors, Growth Factor / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000276:immunology
D000906:Antibodies; D053222:Fas Ligand Protein; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D017978:Receptors, Growth Factor; D000072483:Placenta Growth Factor; D007371:Interferon-gamma; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1