Gliotoxin treatment selectively spares M-CSF- plus IL-3-responsive multipotent haemopoietic progenitor cells in bone marrow.
Gliotoxin, an epipolythiodioxopiperazine, is a fungal metabolite that causes genomic DNA degradation preferentially in certain blood cell types including T lymphocytes and macrophages. Gliotoxin has previously been used to treat murine allogeneic bone marrow prior to transplantation into irradiated recipients, and in this situation the drug prevents development of graft-versus-host disease, and permits the establishment of allogeneic bone marrow chimeras. We have examined the nature of the cells that survive gliotoxin treatment and report here that gliotoxin selectively spares a unique class of haemopoietic stem cell that forms large (HPP) colonies in the presence of mixtures of M-CSF and IL-3. We confirm that the cells which survive gliotoxin treatment are capable of reconstituting the haemopoietic system in allogeneic lethally irradiated mice.
Kobayashi
M
M
Division of Clinical Sciences, John Curtin School of Medical Research, Australian National University, Canberra.
Müllbacher
A
A
Waring
P
P
Hapel
A J
AJ
D000818:Animals; D001854:Bone Marrow Cells; D003114:Colony-Forming Units Assay; D004247:DNA / Q000378:metabolism; D005912:Gliotoxin / Q000494:pharmacology*; D006098:Granulocytes / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D007377:Interleukin-3 / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA
D007377:Interleukin-3; D005912:Gliotoxin; D016173:Macrophage Colony-Stimulating Factor; D004247:DNA