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Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
Selective resistance of bone marrow-derived hemopoietic progenitor cells to gliotoxin
Abstract:
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.
Insights
The fungal toxin gliotoxin damages DNA in mature lymphocytes but spares resistant bone marrow cells. Gliotoxin-treated bone marrow delayed graft-versus-host disease in mice.
Area of Science:
- Immunology
- Molecular Biology
- Hematology
Background:
- The fungal metabolite gliotoxin inhibits mature lymphocyte stimulation by causing genomic DNA degradation.
- Bone marrow contains a subpopulation of cells resistant to gliotoxin's DNA-damaging effects.
Purpose of the Study:
- To investigate the differential effects of gliotoxin on lymphocytes and bone marrow cells.
- To evaluate the potential of gliotoxin-resistant bone marrow cells in managing graft-versus-host disease.
Main Methods:
- Assessing gliotoxin's impact on lymphocyte mitogen stimulation and DNA integrity.
- Identifying and characterizing gliotoxin-resistant cell populations within bone marrow.
- Evaluating the therapeutic potential of gliotoxin-treated bone marrow in allogeneic bone marrow chimeras.
Main Results:
- Gliotoxin induced genomic DNA degradation in mature lymphocytes, inhibiting their response to mitogens.
- A subpopulation of hemopoietic progenitor cells in bone marrow demonstrated resistance to gliotoxin.
- Treatment with gliotoxin-conditioned lymph node cell-enriched bone marrow significantly delayed graft-versus-host disease onset in allogeneic chimeras.
Conclusions:
- Gliotoxin exhibits selective toxicity towards lymphocytes while sparing bone marrow progenitor cells.
- Gliotoxin-resistant bone marrow cells hold promise for mitigating graft-versus-host disease, a critical complication in bone marrow transplantation.
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