Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thymus humoral factor-gamma 2 (THF gamma 2), an octapeptide important for T-lymphocyte regulation, was assessed for its effect on the in vitro growth of human hematopoietic progenitor cells. This was achieved using a recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF)-stimulated myeloid cell colony formation (granulocyte-macrophage colony-forming cells, GM-CFC) assay as well as a recombinant erythropoietin (rEpo)-stimulated erythroid burst formation (erythroid burst-forming units, BFU-E) assay. Cells were obtained from bone marrow (BM) and peripheral blood (PB) of normal healthy donors and from patients with suppressed bone marrows. The latter group included aplastic anemia, leukemia, and lymphoma patients and patients with solid tumors who responded to intensive chemotherapy with significant pancytopenia. THF gamma 2 significantly enhanced normal BM and PB GM-CFC and PB BFU-E by 2- to 2.5-fold. This effect was totally dependent on the presence of the respective growth factors, that is, rGM-CSF or rEpo, and was specifically reversed by an anti-THF gamma 2 antiserum. Furthermore, although THF gamma 2-induced enhancement of GM-CFC colony formation was not affected by lymphocyte or monocyte depletion, the augmenting effect of the peptide on BFU-E was completely abrogated in the absence of lymphocytes. THF gamma 2-induced augmented growth of progenitor cells derived from severely suppressed marrows was minimal. However, cells from moderately neutropenic patients with leukemia in remission or with lymphoma under chemotherapy responded to the peptide similarly to cells from normal donors. These results suggest a stimulatory role for THF gamma 2 on human myeloid and erythroid hematopoietic progenitor cells. They also suggest the lymphocyte dependence of BFU-E enhancement and lymphocyte independence of GM-CFC stimulation by THF gamma 2. In the former case the thymus-derived peptide may act through the induction of certain erythroid-enhancing lymphokines.
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PMID:Thymic humoral factor-gamma 2, an immunoregulatory peptide, enhances human hematopoietic progenitor cell growth. 154 85

Methotrexate (MTX) acts by inducing cellular depletion of reduced folates, which ultimately leads to an inhibition of DNA synthesis. Like many anticancer drugs, this antimetabolite has little selectivity for tumor cells, and its effectiveness is limited by toxicity to normal tissues, particularly gastrointestinal epithelium and bone marrow. Previous studies have shown that MTX inhibits colony formation of the hematopoietic progenitor cells (CFU-C) in vitro. Whether this effect is due to a cytotoxic or a cytostatic mechanism has not been resolved. The present study was undertaken to eludicate the mechanism by which MTX inhibits CFU-C formation. Bone marrow cells in agarose cultures supplemented with recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF) were incubated for 7 days in the presence or absence of MTX. Exposure to 33 nM to 1 microM MTX reduced colony formation by more than 80% when compared to control cultures. When bone marrow suspension cultures supplemented with rmGM-CSF were incubated for 5 days in the presence or absence of MTX, exposure to 10 nM to 1 microM MTX resulted in a 60 to 80% reduction in cell numbers when compared to untreated cultures. Residual CFU-C numbers were determined in the same cultures by replating into agarose. Exposure to 10 nM MTX was found to enhance CFU-C recovery three-fold as compared to controls and cultures exposed to higher MTX concentrations. Addition of 10 microM of the reduced folate leucovorin (LV; 5-formyl-tetrahydrofolate) prevented CFU-C accumulation in the presence of 10 nM MTX. The kinetics of LV rescue of CFU-C, pre-exposed to 100 nM MTX, were investigated in clonogenic assays. The addition of 1 microM LV to semisolid bone marrow cultures preincubated with 100 nM MTX for up to 8 days completely abolished the inhibition of colony formation seen with 100 nM MTX alone. When the dose range of MTX was expanded from 33 nM to 3.3 microM, we found that administration of 10 microM LV on day 5 rescued the hematopoietic progenitors from MTX inhibition in all groups. These observations suggest that MTX is not cytotoxic to hematopoietic progenitors over its entire dose range but that it can induce a reversible block in the proliferation and differentiation of cells in the progenitor compartment.
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PMID:Effect of methotrexate on murine bone marrow cells in vitro: evidence of a reversible antiproliferative action. 772 Aug 15