scholarly journals Hematopoiesis in 5-Fluorouracil-Treated Adenosine A3 Receptor Knock-Out Mice

2015 ◽  
pp. 255-262
Author(s):  
M. HOFER ◽  
M. POSPÍŠIL ◽  
L. DUŠEK ◽  
D. KOMŮRKOVÁ

The purpose of the study was to describe and compare normal and 5-fluorouracil (5-FU)-suppressed hematopoiesis in adenosine A3 receptor knock-out (A3AR KO) mice and their wild-type (WT) counterparts. To meet the purpose, a complex hematological analysis comprising nineteen peripheral blood and bone marrow parameters was performed in the mice. Defects previously observed in the peripheral blood erythrocyte and thrombocyte parameters of the A3AR KO mice were confirmed. Compartments of the bone marrow progenitor cells for granulocytes/macrophages and erythrocytes were enhanced in the control, as well as in the 5-FU-administered A3AR KO mice. 5-FU-induced hematopoietic suppression, evaluated on day 2 after the administration of the cytotoxic drug, was found to be significantly deeper in the A3AR KO mice compared with their WT counterparts, as measured at the level of the bone marrow progenitor cells. The rate of regeneration, as assessed between days 2 and 7 after 5-FU administration, was observed in the population of the granulocyte/macrophage progenitor cells to be higher in the A3AR KO mice in comparison with the WT ones. The increased depth of 5-FU-induced suppression in the compartments of the hematopoietic progenitor cells in the A3AR KO mice represents probably a hitherto undescribed further consequence of the lack of adenosine A3 receptors and indicates its synergism with the pharmacologically induced cytotoxic action of 5-FU.

1993 ◽  
Vol 10 (4-5) ◽  
pp. 405-406 ◽  
Author(s):  
John Nemunaitis ◽  
Vincent Albo ◽  
Zella R. Zeigler ◽  
Richard K. Shadduck ◽  
Craig S. Rosenfeld

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Goutham Vasam ◽  
Shrinidh Joshi ◽  
Sean Thatcher ◽  
Lisa A Cassis ◽  
Yagna P Jarajapu

Angiotensin (Ang)-(1-7)/Mas receptor (MasR) pathway accelerates vascular repair in ischemic conditions partly by stimulating the mobilization of vascular reparative bone marrow progenitor cells (BMPCs) into blood circulation. This study tested if the endogenous MasR expression is required for the mobilization of BMPCs in response to ischemic injury. Hind limb ischemia (HLI) was induced in wild type (WT) or MasR knock out mice (MasR-KO) (in C57Bl/6J background). BMPCs in the blood circulation were quantitated by flow cytometric enumeration of Lineage - , Sca-1 + and cKit + (LSK) cells in peripheral blood or by colony forming unit (CFU) assay. Subcutaneous osmotic pumps were used for continuous infusion of Ang-(1-7) at the rate of 1 μg/kg/min for four weeks. In vitro migration of LSK cells in response to hypoxia-regulated factors, stromal-derived factor (SDF) or by vascular endothelial growth factor (VEGF) were determined. In WT mice, HLI stimulated mobilization of LSK cells that reached maximum by day 2 (110±11 cells/mL blood, n=6). Ang-(1-7)-treatment potentiated the peak mobilization (206±24 cells/mL blood, n=8, P<0.01 compared to the untreated). MasR-KO mice have reduced number of circulating LSKs (12±3 vs 43±9 per mL blood in WT, P<0.01, n=5) (CFUs/mL blood 28±5 vs 54±8 in WT, P<0.05, n=5). In MasR-KO mice, HLI did not induce mobilization, and blood flow recovery post-HLI was lower compared to WT (52±4% vs 89±6% in WT, P<0.001, n=5), both of which were not improved by treatment with Ang-(1-7). Number of bone marrow-resident LSK cells was higher in MasR-KO mice compared to WT. Migration induced by SDF (84±6% vs 160±8% in WT, P<0.001, n=5) or VEGF (97±4% vs 146±5% in WT, P<0.001, n=4) was decreased in MasR-KO. These results suggest that MasR deficiency causes impaired mobilization of BMPCs likely by decreasing their sensitivity to hypoxia-regulated factors. Therefore endogenous MasR expression is essential for ischemia-dependent mobilization of BMPCs.


1996 ◽  
Vol 60 (1) ◽  
pp. 37-43 ◽  
Author(s):  
A. T. Ichiki ◽  
L. A. Gibson ◽  
T. L. Jago ◽  
K. M. Strickland ◽  
D. L. Johnson ◽  
...  

2004 ◽  
Vol 95 ◽  
pp. S69-S70
Author(s):  
M. Giacca ◽  
S. Zacchigna ◽  
N. Arsic ◽  
L. Zentilin ◽  
L. Pattarini ◽  
...  

2007 ◽  
Vol 358 (1) ◽  
pp. 317-324 ◽  
Author(s):  
Emile R. Mohler ◽  
Yun Fang ◽  
Rebecca Gusic Shaffer ◽  
Jonni Moore ◽  
Robert L. Wilensky ◽  
...  

1992 ◽  
Vol 30 (4) ◽  
pp. 559-560
Author(s):  
R. DE BOCK ◽  
D. VAN BOCKSTAELE ◽  
H. SNOECK ◽  
F. LARDON ◽  
M. PEETERMANS

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