Fibrinogen potentiates the effect of interleukin-3 on early human hematopoietic progenitors.
The effect of human fibrinogen on the proliferation of purified SBA- CD34+ human bone marrow progenitors was investigated in clonal cultures. Fibrinogen alone or in combination with erythropoietin had no significant effect. However, in the presence of recombinant human interleukin-3 (IL-3), fibrinogen increased significantly in a dose-dependent manner the number of mixed and burst-forming unit-ethrocyte--derived colonies, whereas the number of other colonies did not significantly change. In the presence of fibrinogen, low concentrations of IL-3 (0.17 U/mL) produced three times more mixed colonies than without fibrinogen, reaching the number of colonies obtained with optimal concentrations of IL-3 (1.67 U/mL). Fibrinogen fragment D had the same effect in the presence of IL-3 as intact fibrinogen, whereas fibrinogen fragment E and human collagen IV did not. This effect was not mediated by integrins, because peptides or monoclonal antibodies that block fibrinogen binding on integrins alpha IIb beta 3, alpha v beta 3 (RGD-peptides), alpha m beta 2 (OKM-1), and alpha x beta 2 (HC1/1) did not affect the observed mitogenic effect. The mitogenic effect of fibrinogen and its D fragment was not mediated by induction of IL-6 or granulocyte--colony-stimulating factor secretion, because it was not inhibited by blocking antisera against these two growth factors. Our results indicate that fibrinogen potentiates the effect of IL-3 on primitive hematopoietic progenitors and suggest that the mitogenic effect of fibrinogen could be mediated via a specific mitogenic receptor that does not belong to the integrin family.
Zhou
Y Q
YQ
Laboratoire de Biologie Cellulaire et Moléculaire des Facteurs de Croissance, Centre National de la Recherche Scientifique, Villejuif, France.
Levesque
J P
JP
Hatzfeld
A
A
Cardoso
A A
AA
Li
M L
ML
Sansilvestri
P
P
Hatzfeld
J
J
D000595:Amino Acid Sequence; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D004921:Erythropoietin / Q000494:pharmacology; D005340:Fibrinogen / Q000008:administration & dosage*; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000502:physiology; D007377:Interleukin-3 / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology
D016023:Integrins; D007377:Interleukin-3; D015850:Interleukin-6; D009842:Oligopeptides; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D005340:Fibrinogen