caa a22 4500 467952116 CHVBK 20180405193743.0 cr unu---uuuuu 170328e20040101xx s 000 0 eng 10.1007/BF02665348 doi (NATIONALLICENCE)springer-10.1007/BF02665348 (NATIONALLICENCE)springer-10.1007/s00280-003-0710-0 Synergistic effects of co-administration of angiotensin 1-7 and Neupogen on hematopoietic recovery in mice [Elektronische Daten] [Dolph Ellefson, Gere diZerega, Theresa Espinoza, Norma Roda, Sonia Maldonado, Kathleen Rodgers] Purpose: Angiotensin 1-7 [A(1-7)] is a seven amino acid peptide that has been shown to increase the proliferation of epidermal stem cells after dermal injury and the number of hematopoietic progenitors in the bone marrow of myelosuppressed mice. In this study, the effect of combining A(1-7) with Neupogen on hematopoietic recovery and bone marrow progenitors was evaluated.Materials and methods: Intravenous 5-fluorouracil (5FU) was administered to induce myelosuppression. Administration of A(1-7) and/or Neupogen was initiated 2 days after chemotherapy. Angiotensin II (AII) and A(1-7) binding were assessed by flow cytometric analysis. Hematopoietic progenitors were counted by colony forming assays. Recovery of formed elements in the blood was evaluated by hemocytometer.Results: Flow cytometric analysis indicated that the number of early hematopoietic progenitors (Lin−Scal+cKit+) that bind AII or A(1-7) incrased 5-7 days after intravenous injection of 150 mg/kg 5FU. Further, administration of A(1-7) led to a slight increase in the number of circulating leukocytes and platelets after this chemotherapeutic regimen. When given in combination with a subclinical dose of Neupogen, a synergistic effect on the number of ciruclating leukocytes was observed, but there was no further effect on the number of circulating platelets. In myelosuppressed mice, A(1-7) had its most profound effect on the number of hematopoietic progenitors in the bone marrow. The progenitors evaluated in the study included BFU-E, CFU-Meg, CFU-GM and CFU-GEMM. There was an increase in the number of these progenitors in the bone marrow, indicating an effect on all hematopoietic lineages. When given in combination with Neupogen, these effects were synergistic for the numbers of BFU-E and CFU-Meg (Neupogen by itself had no effect) and for the myeloid progenitors at lower doses of A(1-7).Conclusions: These results suggest that these hematopoietic agents act at different sites within the hematopoietic cascade and that combining these two agents may be of benefit in the treatment of hematopoietic disorders. Springer-Verlag, 2003 Filgrastim Hematopoietic recovery nationallicence Angiotensin 1-7 nationallicence Synergistic effects nationallicence Hematopoietic recovery nationallicence Filgrastim nationallicence Ellefson Dolph 1321 N. Mission Road, 90033, Los Angeles, CA, USA aut diZerega Gere 1321 N. Mission Road, 90033, Los Angeles, CA, USA aut Espinoza Theresa 1321 N. Mission Road, 90033, Los Angeles, CA, USA aut Roda Norma 1321 N. Mission Road, 90033, Los Angeles, CA, USA aut Maldonado Sonia 1321 N. Mission Road, 90033, Los Angeles, CA, USA aut Rodgers Kathleen 1321 N. Mission Road, 90033, Los Angeles, CA, USA aut Cancer Chemotherapy and Pharmacology Springer-Verlag 53/1(2004-01-01), 15-24 0344-5704 53:1<15 2004 53 280 https://doi.org/10.1007/BF02665348 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02665348 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ellefson Dolph 1321 N. Mission Road, 90033, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- diZerega Gere 1321 N. Mission Road, 90033, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- Espinoza Theresa 1321 N. Mission Road, 90033, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- Roda Norma 1321 N. Mission Road, 90033, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- Maldonado Sonia 1321 N. Mission Road, 90033, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- Rodgers Kathleen 1321 N. Mission Road, 90033, Los Angeles, CA, USA aut NATIONALLICENCE 773 0- Cancer Chemotherapy and Pharmacology Springer-Verlag 53/1(2004-01-01), 15-24 0344-5704 53:1<15 2004 53 280 NATIONALLICENCE 700 1- Ellefson Dolph University of Southern California, Keck School of Medicine, 1321N. Mission Road, CA 90033, Los Angeles, USA aut NATIONALLICENCE 700 1- diZerega Gere University of Southern California, Keck School of Medicine, 1321N. Mission Road, CA 90033, Los Angeles, USA aut NATIONALLICENCE 700 1- Espinoza Theresa University of Southern California, Keck School of Medicine, 1321N. Mission Road, CA 90033, Los Angeles, USA aut NATIONALLICENCE 700 1- Roda Norma University of Southern California, Keck School of Medicine, 1321N. Mission Road, CA 90033, Los Angeles, USA aut NATIONALLICENCE 700 1- Maldonado Sonia University of Southern California, Keck School of Medicine, 1321N. Mission Road, CA 90033, Los Angeles, USA aut NATIONALLICENCE 700 1- Rodgers Kathleen University of Southern California, Keck School of Medicine, 1321N. Mission Road, CA 90033, Los Angeles, USA aut NATIONALLICENCE 856 40 https://doi.org/10.1007/s00280-003-0710-0 text/html Onlinezugriff via DOI Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE NATIONALLICENCE NL-springer