Influence of IL-1 alpha and -1 beta on the survival of human bone marrow cells responding to hematopoietic colony-stimulating factors.
Purified recombinant human (rhu) IL-1 alpha and IL-1 beta were evaluated for their effects on the proliferation and survival of granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) progenitor cells from normal human bone marrow (BM). Using nonadherent low density T lymphocyte depleted (NALT-) BM cells cultured in the presence or absence of IL-1, CSF-deprivation studies demonstrated that IL-1 alpha or IL-1 beta by itself did not enhance the proliferation of CFU-GM or BFU-E. They did, however, promote the survival of progenitors responding to the delayed addition of media conditioned by the 5637 cell line (5637 conditioned medium), rhu GM-CSF and erythropoietin. The survival promoting effects of IL-1 alpha on CFU-GM and BFU-E were neutralized by anti-IL-1 alpha mAb added to the cultures. The survival promoting effect of IL-1 alpha did not appear to be mediated by CSF, because neither CSF nor erythroid burst promoting activity were detectable in cultures in which NALT- cells were incubated with rhuIL-1 alpha. In addition, suboptimal concentrations of rhu macrophage CSF (CSF-1), G-CSF, GM-CSF, and IL-3, which were just below the levels that would stimulate colony formation, did not enhance progenitor cell survival. Survival of CFU-GM and BFU-E in low density (LD) bone marrow cells did not decrease as drastically as that in NALT- BM cells, and exogenously added IL-1 did not enhance progenitor cell survival of CFU-GM and BFU-E in LD BM cells. However, addition of anti-IL-1 beta decreased survival of CFU-GM and BFU-E in LD BM cells. These results implicate IL-1 in the prolonged survival of human CFU-GM and BFU-E.
Hangoc
G
G
Department of Medicine, Indiana University School of Medicine, Indianapolis 46223.
Williams
D E
DE
Falkenburg
J H
JH
Broxmeyer
H E
HE
D000911:Antibodies, Monoclonal / Q000502:physiology; D001853:Bone Marrow / Q000276:immunology* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D004900:Erythroblasts / Q000502:physiology; D004921:Erythropoietin / Q000494:pharmacology; D006098:Granulocytes / Q000502:physiology; D006133:Growth Substances / Q000494:pharmacology*; D016298:Hematopoietic Cell Growth Factors; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D007958:Leukocyte Count; D008212:Lymphocyte Depletion; D008264:Macrophages / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D016298:Hematopoietic Cell Growth Factors; D007375:Interleukin-1; D011994:Recombinant Proteins; D004921:Erythropoietin