Abrogation of radiation injury to human hematopoietic stem cells with tumor necrosis factor-alpha.
Ionizing radiation kills hematopoietic stem and progenitor cells. However, several cytokines, including tumor necrosis factor-alpha (TNF-alpha), protect the murine hematopoietic system if they are introduced before or immediately after irradiation. We examined the in vitro capacity of TNF-alpha to protect human hematopoietic stem cells and early progenitor cells from x-ray-induced death. Human CD34+ cells obtained from normal bone marrow were highly enriched for stem and progenitor cells. Pulse exposure of these cells to human TNF-alpha during the first hour immediately after x irradiation (doses of 0.45 Gy to 9 Gy) significantly improved further survival of true hematopoietic stem cells and early progenitors and the ability of CD34+ cells to produce mature hematopoietic cells in liquid culture with hematopoietic growth factors. The radioprotective effect of TNF-alpha was stronger at lower doses, when complete restoration of hematopoiesis was often observed. In contrast, the radioprotective effect of TNF-alpha was moderate at higher doses, with neither complete restoration of the number of stem and progenitor cells nor the production of mature cells. Our data suggest that TNF-alpha can protect human hematopoietic stem and early progenitor cells from ionizing radiation.
Karkanitsa
L V
LV
Republican Children Oncohematological Center, Minsk, Belarus.
Komarovskaya
M E
ME
Krivenko
S I
SI
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology / Q000528:radiation effects; D002470:Cell Survival; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004307:Dose-Response Relationship, Radiation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects*; D006801:Humans; D007739:L Cells; D051379:Mice; D011837:Radiation-Protective Agents; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014965:X-Rays
D015703:Antigens, CD; D018952:Antigens, CD34; D011837:Radiation-Protective Agents; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha