In vivo modulation of myelopoiesis by prostaglandin E2. II. Inhibition of granulocyte-monocyte progenitor cell (CFU-GM) cell-cycle rate

P. S. Gentile, Louis Pelus

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Abstract

The effects of in vivo administration of native prostaglandin E2 (PGE) on the cycling status of the granulocyte-monocyte progenitor cell (CFU-GM) were examined in a mouse model. In mice hematopoietically rebounding from a sublethal dose of cyclophosphamide, intravenous injection of PGE in doses ranging from 100 to 10-4 μg/mouse/day over three days, significantly decreased the absolute number of CFU-GM per femur and the percentage of CFU-GM in the S-phase of the cell cycle. Administration of PGE2, 10 μg/mouse/day, over three days to steady-state mice resulted in significant suppression of the absolute number of CFU-GM per femur, but was without effect on CFU-GM cycling. However, when an additional PGE2 injection was included on day 4 and mice killed 6 h later, inhibition of both parameters was observed. Single bolus injection of PGE2 into steady-state mice was found to have the identical effect. Inhibition of the absolute number of CFU-GM per femur and percentage of CFU-GM in S-phase was apparent 6 h after injection of a single dose of 10 μg PGE, with a loss of effect on CFU-GM cycling status 12-14 h after injection. The inhibitory effect of PGE2 on the absolute number of CFU-GM per femur persisted for two days after injection. These studies confirmed the cell-cycle effects of PGE, heretofore demonstrated only in vitro; illustrated the importance of timing and dose analysis when examining the effects of hematopoietic inhibitors in vivo; and suggested that PGE2 may be useful as an adjunct to chemotherapy in ameliorating myelotoxicity. Furthermore, dose-response analysis revealed an enhanced in vivo sensitivity of macrophage progenitor cells (M-CFC) to the inhibitory effects of injected PGE2. Inhibition of in vivo incorporation of tritiated thymidine (3HTdr) into bone marrow CFU-GM by PGE could also be demonstrated.

Original languageEnglish (US)
Pages (from-to)119-126
Number of pages8
JournalExperimental Hematology
Volume15
Issue number2
StatePublished - 1987
Externally publishedYes

Fingerprint

Myelopoiesis
Granulocyte Precursor Cells
Granulocyte-Macrophage Progenitor Cells
Dinoprostone
Monocytes
Cell Cycle
Femur
Injections
S Phase
Intravenous Injections
Cyclophosphamide
Thymidine
Stem Cells

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

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title = "In vivo modulation of myelopoiesis by prostaglandin E2. II. Inhibition of granulocyte-monocyte progenitor cell (CFU-GM) cell-cycle rate",
abstract = "The effects of in vivo administration of native prostaglandin E2 (PGE) on the cycling status of the granulocyte-monocyte progenitor cell (CFU-GM) were examined in a mouse model. In mice hematopoietically rebounding from a sublethal dose of cyclophosphamide, intravenous injection of PGE in doses ranging from 100 to 10-4 μg/mouse/day over three days, significantly decreased the absolute number of CFU-GM per femur and the percentage of CFU-GM in the S-phase of the cell cycle. Administration of PGE2, 10 μg/mouse/day, over three days to steady-state mice resulted in significant suppression of the absolute number of CFU-GM per femur, but was without effect on CFU-GM cycling. However, when an additional PGE2 injection was included on day 4 and mice killed 6 h later, inhibition of both parameters was observed. Single bolus injection of PGE2 into steady-state mice was found to have the identical effect. Inhibition of the absolute number of CFU-GM per femur and percentage of CFU-GM in S-phase was apparent 6 h after injection of a single dose of 10 μg PGE, with a loss of effect on CFU-GM cycling status 12-14 h after injection. The inhibitory effect of PGE2 on the absolute number of CFU-GM per femur persisted for two days after injection. These studies confirmed the cell-cycle effects of PGE, heretofore demonstrated only in vitro; illustrated the importance of timing and dose analysis when examining the effects of hematopoietic inhibitors in vivo; and suggested that PGE2 may be useful as an adjunct to chemotherapy in ameliorating myelotoxicity. Furthermore, dose-response analysis revealed an enhanced in vivo sensitivity of macrophage progenitor cells (M-CFC) to the inhibitory effects of injected PGE2. Inhibition of in vivo incorporation of tritiated thymidine (3HTdr) into bone marrow CFU-GM by PGE could also be demonstrated.",
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AU - Gentile, P. S.

AU - Pelus, Louis

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N2 - The effects of in vivo administration of native prostaglandin E2 (PGE) on the cycling status of the granulocyte-monocyte progenitor cell (CFU-GM) were examined in a mouse model. In mice hematopoietically rebounding from a sublethal dose of cyclophosphamide, intravenous injection of PGE in doses ranging from 100 to 10-4 μg/mouse/day over three days, significantly decreased the absolute number of CFU-GM per femur and the percentage of CFU-GM in the S-phase of the cell cycle. Administration of PGE2, 10 μg/mouse/day, over three days to steady-state mice resulted in significant suppression of the absolute number of CFU-GM per femur, but was without effect on CFU-GM cycling. However, when an additional PGE2 injection was included on day 4 and mice killed 6 h later, inhibition of both parameters was observed. Single bolus injection of PGE2 into steady-state mice was found to have the identical effect. Inhibition of the absolute number of CFU-GM per femur and percentage of CFU-GM in S-phase was apparent 6 h after injection of a single dose of 10 μg PGE, with a loss of effect on CFU-GM cycling status 12-14 h after injection. The inhibitory effect of PGE2 on the absolute number of CFU-GM per femur persisted for two days after injection. These studies confirmed the cell-cycle effects of PGE, heretofore demonstrated only in vitro; illustrated the importance of timing and dose analysis when examining the effects of hematopoietic inhibitors in vivo; and suggested that PGE2 may be useful as an adjunct to chemotherapy in ameliorating myelotoxicity. Furthermore, dose-response analysis revealed an enhanced in vivo sensitivity of macrophage progenitor cells (M-CFC) to the inhibitory effects of injected PGE2. Inhibition of in vivo incorporation of tritiated thymidine (3HTdr) into bone marrow CFU-GM by PGE could also be demonstrated.

AB - The effects of in vivo administration of native prostaglandin E2 (PGE) on the cycling status of the granulocyte-monocyte progenitor cell (CFU-GM) were examined in a mouse model. In mice hematopoietically rebounding from a sublethal dose of cyclophosphamide, intravenous injection of PGE in doses ranging from 100 to 10-4 μg/mouse/day over three days, significantly decreased the absolute number of CFU-GM per femur and the percentage of CFU-GM in the S-phase of the cell cycle. Administration of PGE2, 10 μg/mouse/day, over three days to steady-state mice resulted in significant suppression of the absolute number of CFU-GM per femur, but was without effect on CFU-GM cycling. However, when an additional PGE2 injection was included on day 4 and mice killed 6 h later, inhibition of both parameters was observed. Single bolus injection of PGE2 into steady-state mice was found to have the identical effect. Inhibition of the absolute number of CFU-GM per femur and percentage of CFU-GM in S-phase was apparent 6 h after injection of a single dose of 10 μg PGE, with a loss of effect on CFU-GM cycling status 12-14 h after injection. The inhibitory effect of PGE2 on the absolute number of CFU-GM per femur persisted for two days after injection. These studies confirmed the cell-cycle effects of PGE, heretofore demonstrated only in vitro; illustrated the importance of timing and dose analysis when examining the effects of hematopoietic inhibitors in vivo; and suggested that PGE2 may be useful as an adjunct to chemotherapy in ameliorating myelotoxicity. Furthermore, dose-response analysis revealed an enhanced in vivo sensitivity of macrophage progenitor cells (M-CFC) to the inhibitory effects of injected PGE2. Inhibition of in vivo incorporation of tritiated thymidine (3HTdr) into bone marrow CFU-GM by PGE could also be demonstrated.

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