title: Effects of recombinant human tumor necrosis factor (rhTNF) on normal human and mouse hemopoietic progenitor cells.
abstract: We examined the effects of recombinant human tumor necrosis factor (rhTNF) on normal human and murine granulocyte-macrophage (CFU-gm) and erythroid (CFU-e, BFU-e) progenitor cells. We suppressed in vitro colony formation by human marrow CFU-gm, CFU-e and BFU-e or peripheral blood BFU-e by adding rhTNF to the culture in a dose-related manner. A half-maximal inhibition was observed with 1-10 ng/ml. Leukemic cell line K562 cells were found to be sensitive to rhTNF in the clonogenic colony assay. However, the clonal growth of murine marrow CFU-e and BFU-e colonies was less than 50% inhibited and CFU-gm growth was unaffected even at a concentration of 1,000 ng/ml. We observed slight to moderate inhibition after 24 h pulse exposure of both human and murine-committed progenitors to rhTNF prior to the culture. Intravenous injection of 1 mg/kg of rhTNF caused a marked decrease in marrow erythroid progenitors and consequently caused anemia in the mice. Our data indicate that rhTNF has a suppressive effect on normal human and murine hemopoietic colony formation in vitro and murine erythropoiesis in vivo.
authors.forename: K
authors.initials: K
authors.lastname: Akahane
authors.forename: T
authors.initials: T
authors.lastname: Hosoi
authors.forename: A
authors.initials: A
authors.lastname: Urabe
authors.forename: M
authors.initials: M
authors.lastname: Kawakami
authors.forename: F
authors.initials: F
authors.lastname: Takaku
mesh_terms: D000818:Animals; D002460:Cell Line; D003114:Colony-Forming Units Assay; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D014409:Tumor Necrosis Factor-alpha
chemical_list: D006023:Glycoproteins; D014409:Tumor Necrosis Factor-alpha