Tumor necrosis factor-alpha and TNF-beta inhibit clonogenicity of mobilized human hematopoietic progenitors

We studied the effect of tumor necrosis factors (TNF-alpha and TNF-beta) on the clonogenicity of peripheral blood progenitor cells (PBPC) mobilized by granulocyte colony-stimulating factor (G-CSF). The cells were obtained by nine leukaphereses in patients with malignancies undergoing peripheral blood stem cell transplantation (PBSCT). Flow cytometry was performed to evaluate the number of CD34+ cells in peripheral blood and leukapheresis products. PBPC were grown in semisolid medium supplemented with human growth factors in the absence or presence of TNF at concentrations ranging from 0.1 to 10 ng/ml. Colonies were scored on day 14. TNF-alpha and TNF-beta suppressed colony formation in all cases studied. TNF-alpha inhibited the growth of colony-forming units-granulocyte-macrophage (CFU-GM) at 1 and 10 ng/ml and burst-forming units-erythroid (BFU-E) at 10 ng/ml (p < 0.05), and TNF-beta inhibited the growth of CFU-GM and BFU-E at 1 and 10 ng/ml (p < 0.05). Thus, G-CSF-mobilized hematopoietic PBPC are highly sensitive to both TNF-alpha and TNF-beta. This finding should be taken in account when PBPC are handled ex vivo.