Transforming growth factor beta (TGF-beta), a potent inhibitor of erythropoiesis: neutralizing TGF-beta antibodies show erythropoietin as a potent stimulator of murine burst-forming unit erythroid colony formation in the absence of a burst-promoting activity.
Transforming growth factor beta (TGF-beta) is a bifunctional regulator of the growth of myeloid progenitors and is here demonstrated to directly inhibit the growth of primitive erythroid progenitors by 95% to 100% regardless of the cytokines stimulating growth. Autocrine TGF-beta production of primitive hematopoietic progenitors has previously been reported. In the present study, a neutralizing TGF-beta antibody (anti-TGF-beta) added to serum-containing cultures, resulted in a 3-, 4-, and 25-fold increase in burst-forming unit erythroid (BFU-E) colony formation in response to interleukin-4 (IL-4) plus erythropoietin (Epo), SCF plus Epo, and IL-11 plus Epo, respectively. The growth of BFU-E progenitors has been suggested to require a burst-promoting activity in addition to Epo. Accordingly, we observed no BFU-E colony formation in serum-containing cultures in response to Epo alone. In contrast, 50 BFU-E colonies were formed when anti-TGF-beta was included in the culture. In serum-free cultures, Epo also stimulated BFU-E colony formation in the absence of other cytokines, whereas anti-TGF-beta had no effect on the number of colonies formed. Quantitation of TGF-beta 1 in serum by an enzyme-linked immunosorbent assay method showed predominantly the presence of precursor (latent) TGF-beta 1, but also showed active TGF-beta 1 at a concentration sufficient to potently inhibit erythroid colony formation. Thus, neutralization of active TGF-beta 1 in serum shows that Epo alone is sufficient to stimulate the growth of murine BFU-E progenitors.
Dybedal
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Institute of Cancer Research, University of Trondheim, Norway.
Jacobsen
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D000818:Animals; D000937:Antigen-Antibody Reactions; D001854:Bone Marrow Cells; D003470:Culture Media; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000502:physiology*; D006098:Granulocytes / Q000166:cytology; D006410:Hematopoiesis / Q000187:drug effects; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology; D051379:Mice; D019089:Stem Cell Factor; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D003470:Culture Media; D016298:Hematopoietic Cell Growth Factors; D019089:Stem Cell Factor; D016212:Transforming Growth Factor beta; D004921:Erythropoietin