Live attenuated Salmonella carrying platelet factor 4 cDNAs as radioprotectors.
To determine whether live attenuated Salmonella carrying platelet factor 4 cDNAs can protect mice from radiation damage, the attenuated Salmonella SL3261 was used as oral vector for targeted gene delivery. The recovery of mice receiving sublethal total-body irradiation (TBI) was investigated after the oral administration of attenuated Salmonella carrying cDNA for platelet factor 4 (PF4) or truncated PF4. This oral gene therapy protected mice from radiation damage after TBI. The number of bone marrow cells and high proliferative potential colony-forming cells (HPP-CFCs) increased significantly at day 7. Similarly, the administration of PF4 or PF4(17-70) protein also improved the survival of mice after TBI. Both PF4 gene therapy and protein administration accelerated hematopoietic recovery in vivo in mice after irradiation. In vitro, PF4 also promoted survival and proliferation of 5-fluorouracil-resistant hematopoietic stem/progenitor cells after irradiation. These data demonstrate a novel biological function of PF4 as a protector against radiation injury and suggest that attenuated Salmonella could be used in vivo as a PF4 DNA delivery vector in the management of radiation injury.
Liu
Bin
B
State Key Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, PR of China.
Zhao
Lihua
L
Yu
Xiaofei
X
Han
Zhibo
Z
Lu
Shihong
S
Yang
Renchi
R
Han
Zhong Chao
ZC
D000284:Administration, Oral; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010978:Platelet Factor 4 / Q000235:genetics* / Q000378:metabolism*; D011832:Radiation Injuries / Q000235:genetics / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D012486:Salmonella typhimurium / Q000235:genetics*; D015996:Survival Rate
D018076:DNA, Complementary; D010978:Platelet Factor 4