Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Gliotoxin treatment selectively spares M-CSF- plus IL-3-responsive multipotent haemopoietic progenitor cells in bone marrow. 170 26

The fungal metabolite gliotoxin at low concentrations prevents mitogen stimulation of mature lymphocytes as a result of gliotoxin-induced genomic DNA degradation. Bone marrow, on the other hand, contains a subpopulation of cells resistant to gliotoxin at similar concentrations. This population includes the hemopoietic progenitor cells that grow in vitro in response to appropriate colony-stimulating factors and cells that form colonies in the spleens of lethally irradiated recipients. Gliotoxin treatment of lymph node cell-enriched bone marrow significantly delayed the onset of graft-versus-host disease in fully allogeneic bone marrow chimeras.
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PMID:Selective resistance of bone marrow-derived hemopoietic progenitor cells to gliotoxin. 243 87

Gliotoxin, a secondary fungal metabolite, at nanomolar concentrations, irreversibly inhibits murine T cell proliferation to mitogen. Treatment of allogeneic spleen cells with gliotoxin allows their transfer into sublethally irradiated recipients without inducing a GVH reaction. Gliotoxin treatment of bone marrow allows the establishment of fully allogenic bone marrow chimeras free of GVH disease. The cytotoxic T cell repertoire against influenza virus in these animals is restricted to both host- and donor-type MHC. However, their immune competence is severely compromised by their lack of host MHC-type stimulator cells.
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PMID:Prevention of graft-versus-host disease by treatment of bone marrow with gliotoxin in fully allogeneic chimeras and their cytotoxic T cell repertoire. 245 43

Gliotoxin (GT) is a fungal metabolite that reduces the ability of murine macrophages to react immunologically in vitro. It is also capable of modulating the immunogenicity of murine bone marrow cells, so that the onset of graft-versus-host disease in fully allogeneic bone marrow chimeras is delayed. The present study examines the effect of GT on human fetal cells, both in terms of reduction of immunogenicity and toxicity. GT (10 micrograms/ml) significantly decreased the responsiveness in mixed lymphocyte cultures of cells derived from human fetal pancreas, spleen, liver and bone marrow. This concentration of GT was, however, mildly toxic to explants of the pancreas, with a significant reduction in insulin secretion from this tissue during the first day of its organ culture, but not thereafter. GT-treated pancreatic explants were lighter and contained less insulin than the untreated controls 3 months after the tissue had been implanted beneath the renal capsule of nude mice. This difference was not apparent 3 weeks after transplantation into these animals. It is hypothesized that the immunomodulating effect of GT (at a concentration less than 10 micrograms/ml) may be of benefit in treating allografted human fetal pancreas before it is transplanted, as it has for murine adult bone marrow cells.
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PMID:Immunomodulation of human fetal cells by the fungal metabolite gliotoxin. 248 85

Gliotoxin is an immunosuppressive secondary metabolite produced by several pathogenic fungi. It has previously been shown to prevent graft-versus-host disease in transplantation of allogeneic mouse bone marrow and to reduce the immunogenicity of human fetal pancreas. We here report on the effect of gliotoxin on the prevention of rejection of allografts in two distinct models. Bathing mouse thyroid tissue in gliotoxin solution for 16 hr prolonged graft survival following transplantation into allogeneic recipients. In contrast the perfusion of rat kidneys with gliotoxin followed by 1 hr of incubation before orthotopic transplantation had little success with preventing allograft rejection. This disparity is most likely due to the incubation in the renal model not allowing sufficient time for the elimination of antigen presenting cells in the donor organ. However, the success with the thyroid grafts demonstrates the potential of gliotoxin as an immunomodulating agent in organ transplantation and warrants further investigation in other systems.
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PMID:Investigation of the potential use of immunosuppressive agent gliotoxin in organ transplantation. 749 90