RESUMO
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.
Assuntos
Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos da radiação , Protetores contra Radiação , Fator de Necrose Tumoral alfa/farmacologia , Animais , Antígenos CD/análise , Antígenos CD34/análise , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos da radiação , Sobrevivência Celular , Células Cultivadas , Ensaio de Unidades Formadoras de Colônias , Relação Dose-Resposta à Radiação , Células-Tronco Hematopoéticas/citologia , Humanos , Células L , Camundongos , Proteínas Recombinantes/farmacologia , Raios XRESUMO
The influence of X-radiation on production of interleukin-6 (IL-6) and alpha-tumor necrosis factor (TNF) has been investigated. Irradiation with doses of 45, 90 and 900 cGy was shown to increase considerably TNF and IL-6 production both in intact mononuclear cultures of human peripheral blood and in cultures stimulated by phytohemagglutinin. In addition to an absolute increase in the production, the stimulatory effect was manifested by earlier accumulation of IL-6 and TNF activities in supernatant fractions of the cultures under study.
Assuntos
Interleucina-6/efeitos da radiação , Leucócitos Mononucleares/efeitos da radiação , Fator de Necrose Tumoral alfa/efeitos da radiação , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/metabolismo , Células Cultivadas/efeitos da radiação , Relação Dose-Resposta à Radiação , Humanos , Técnicas In Vitro , Interleucina-6/biossíntese , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Fito-Hemaglutininas/farmacologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/efeitos dos fármacosRESUMO
Human peripheral blood mononuclear cells (PBMC) and monocytes produce a large amount of tumor necrosis factor/cachectin (TNF) in vitro. Our data suggest that X-irradiation can increase TNF production by these cells. After 900 cGy irradiation there were 7-fold (24 h incubation) and 2.3-fold (48 h incubation) increases of TNF production by stimulated PBMC. The irradiation also increased TNF production by both stimulated and unstimulated human monocytes. These findings suggest that TNF overproduction can play an important role in the pathogenesis of radiation disease.
