Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine synergize to enhance haematopoietic reconstitution in irradiated mice
Jazyk angličtina Země Velká Británie, Anglie Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
- MeSH
- adenosin metabolismus MeSH
- adenosinmonofosfát farmakologie MeSH
- dipyridamol farmakologie MeSH
- erytrocyty účinky léků MeSH
- faktor stimulující granulocyto-makrofágové kolonie účinky léků účinky záření MeSH
- faktor stimulující kolonie granulocytů farmakologie MeSH
- granulocyty účinky léků účinky záření MeSH
- hematopoetické kmenové buňky účinky léků účinky záření MeSH
- inhibitory agregace trombocytů farmakologie MeSH
- lymfocyty účinky léků MeSH
- monocyty účinky léků MeSH
- myši inbrední BALB C MeSH
- myši inbrední CBA MeSH
- myši MeSH
- purinergní receptory P1 metabolismus MeSH
- synergismus léků MeSH
- trombocyty účinky léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adenosin MeSH
- adenosinmonofosfát MeSH
- dipyridamol MeSH
- faktor stimulující granulocyto-makrofágové kolonie MeSH
- faktor stimulující kolonie granulocytů MeSH
- inhibitory agregace trombocytů MeSH
- purinergní receptory P1 MeSH
The activation of adenosine receptors has recently been demonstrated to stimulate haematopoiesis. In the present study, we investigated the ability of drugs elevating extracellular adenosine to influence curative effects of granulocyte colony-stimulating factor (G-CSF) in mice exposed to a sublethal dose of 4 Gy of 60Co radiation. Elevation of extracellular adenosine in mice was induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects of dipyridamole plus AMP, and G-CSF, administered either alone or in combination, were evaluated. The drugs were injected to mice in a 4-d treatment regimen starting on d 3 after irradiation and the haematopoietic response was evaluated on d 7, 10, 14, 18 and 24 after irradiation. While the effects of G-CSF on the late maturation stages of blood cells, appearing shortly after the completion of the treatment, were not influenced by dipyridamole plus AMP, positive effects of the combination therapy occurred in the post-irradiation recovery phase which is dependent on the repopulation of haematopoietic stem cells. This was indicated by the significant elevation of counts of granulocyte-macrophage progenitor cells (GM-CFC) and granulocytic cells in the bone marrow (d 14), of GM-CFC (d 14), granulocytic and erythroid cells (d 14 and 18) in the spleen, and of neutrophils (d 18), monocytes (d 14 and 18) and platelets (d 18) in the peripheral blood. These effects suggest that the repopulation potential of the combination therapy lies in a common multilineage cell population. The results of this study implicate the promising possibility to enhance the curative effects of G-CSF under conditions of myelosuppressive states induced by radiation exposure.
Citace poskytuje Crossref.org
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