Protection of cells capable of reconstituting long-term bone marrow stromal cultures from 4-hydroperoxycyclophosphamide by interleukin 1 and tumor necrosis factor.
The cytokines interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) have been implicated in protecting normal hematopoiesis from both irradiation and chemotherapy damage. The mechanism of action of these cytokines and which cells are protected is not known. In this study, we report on the ability of IL-1 and TNF-alpha to protect hematopoietic cells capable of repopulating irradiated long-term bone marrow stromal cultures from 4-hydroperoxycyclophosphamide (4-HC). Irradiated long-term bone marrow cultures recharged with hematopoietic cells pretreated with IL-1 and TNF-alpha prior to 4-HC were shown to give rise to greater numbers of colony-forming cells at 4-5 weeks of culture within both the nonadherent and adherent cell populations of the long-term cultures when compared to controls. These results suggest that IL-1 and TNF-alpha can protect human long-term culture-initiating cells, which are closely related to reconstituting stem cells.
Zucali
J R
JR
Department of Medicine, University of Florida, Gainesville 32610.
Moreb
J
J
Bain
C
C
D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects; D001854:Bone Marrow Cells; D002452:Cell Count; D002478:Cells, Cultured; D003470:Culture Media / Q000009:adverse effects*; D003520:Cyclophosphamide / Q000009:adverse effects / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D003470:Culture Media; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D003520:Cyclophosphamide; C011272:perfosfamide