Erythroblasts are a source of angiogenic factors.
In adult bone marrow, mature erythroblasts are produced within structures called erythroblastic islands and then cross the endothelial barrier to reach circulation. Erythroblastic islands are composed of a central macrophage surrounded by maturing erythroblasts. In this study, it is shown that erythroid cells, but not the other mature hematopoietic cells, coexpress 2 angiogenic factors, vascular endothelial growth factor A (VEGF-A) and placenta growth factor (PlGF). Secretion of both VEGF-A and PlGF increases during in vitro erythroid differentiation. Erythroblast-conditioned medium can induce both migration of monocytes and endothelial cells and the permeability of endothelial cells. These effects are inhibited by anti-PlGF and/or anti-VEGF antibodies. Finally, it is shown that VEGF-A and PlGF proteins are expressed by bone marrow erythroblasts in vivo. Angiogenic factors secreted by erythroblasts may promote interactions either with macrophages in erythroblastic islands or with endothelial cells that would facilitate the passage of erythroid cells through the endothelial barrier. (Blood. 2001;97:1968-1974)
Institut National de la Santé et de la Recherche Médicale (INSERM) U474, Maternité Port-Royal, Paris, France.
R
R
Tordjman
S
S
Delaire
J
J
Plouët
S
S
Ting
P
P
Gaulard
S
S
Fichelson
P H
PH
Roméo
V
V
Lemarchandel
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016895:Culture Media, Serum-Free; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000378:metabolism*; D004920:Erythropoiesis / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019089:Stem Cell Factor / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A
D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D016228:Endothelial Growth Factors; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor