In vivo haemoprotective activity of tetrapeptide AcSDKP combined with granulocyte-colony stimulating factor following sublethal irradiation.
We report that acetyl-N-Ser-Asp-Lys-Pro (AcSDKP), which removes progenitor cells from cell cycle, in combination with granulocyte-colony stimulating factor (G-CSF) can significantly improve myelorestoration following irradiation (7 Gy). Peripheral blood, spleen and bone marrow (BM) cell recovery and progenitor cell reconstitution [IL-3-responsive colony-forming cells (CFC) and high proliferative potential colony-forming cells (HPP-CFC)] were studied. Studies on the optimal schedule of AcSDKP administration revealed maximal effects on progenitor cells when AcSDKP was administered as a continuous infusion for 3 d starting 24 h prior to irradiation and used in combination with G-CSF. The numbers of CFC and HPP-CFC in the BM were significantly increased following irradiation in mice receiving AcSDKP and G-CSF as compared to either drug alone. The numbers of CFC in the spleen were significantly increased in mice receiving AcSDKP and G-CSF on days 10 and 14 as compared to AcSDKP alone, but not G-CSF. Similarly, CFC and HPP-CFC in the spleen were significantly increased in mice receiving AcSDKP and G-CSF on day 18 as compared to mice receiving PBS and G-CSF. These studies suggest that AcSDKP in combination with G-CSF may have potential for the protection of progenitor cells in patients undergoing intensive chemo- and/or radiotherapy.
Watanabe
T
T
Department of Pathology/Microbiology, University of Nebraska Medical Center, Omaha 68198-5660, USA.
Kelsey
L S
LS
Yan
Y
Y
Brown
G S
GS
Jackson
J D
JD
Ewel
C
C
Talmadge
J E
JE
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects; D001854:Bone Marrow Cells; D004338:Drug Combinations; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects / Q000528:radiation effects; D007377:Interleukin-3 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D013234:Stem Cells / Q000187:drug effects / Q000528:radiation effects
D004338:Drug Combinations; D007377:Interleukin-3; D009842:Oligopeptides; D016179:Granulocyte Colony-Stimulating Factor; C058504:goralatide