Oral administration of recombinant human granulocyte-macrophage colony stimulating factor expressed in rice endosperm can increase leukocytes in mice.
Human granulocyte-macrophage colony stimulating factor (hGM-CSF) is used clinically to treat leucopenia typically caused by cancer chemotherapy or radiotherapy. This study used multiple strategies to obtain very high expression levels of OsrhGM-CSF (14 microg/seed) in rice endosperm. Electron micrographs of immunogold-labeled transgenic endosperm showed that rhGM-CSF was not only localized in protein bodies but was also distributed in the apoplast. A biological activity assay indicated that OsrhGM-CSF stimulated the growth of TF-1 cells in vitro. In addition, the transgene was used to effectively treat leucopenia by oral administration of the unprocessed transgenic grains. In cyclophosphamide-induced leucopenic mice, transgenic seeds produced a 27% (t=0.021) gain in leukocytes after 14 days feeding. Even in non-leucopenic mice, leukocyte gain was 37% (t=0.002) more than that of mice fed non-transgenic seeds. This study provides a novel approach to the use of oral unprocessed transgenic OsrhGM-CSF seeds to treat leucopenia.
Ning
Tingting
T
Engineering Research Center for Plant Biotechnology and Germplasm Utilization, Ministry of Education, Department of Genetics, College of Life Sciences, Wuhan University, Wuhan 430072, PR China.
Xie
Tingting
T
Qiu
Qingchuan
Q
Yang
Wei
W
Zhou
Shunquan
S
Zhou
Limei
L
Zheng
Congyi
C
Zhu
Yingguo
Y
Yang
Daichang
D
D000284:Administration, Oral; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D003001:Cloning, Molecular; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000494:pharmacology*; D006801:Humans; D007958:Leukocyte Count; D007962:Leukocytes / Q000166:cytology* / Q000187:drug effects*; D007970:Leukopenia / Q000473:pathology; D008297:Male; D051379:Mice; D009928:Organ Specificity / Q000187:drug effects; D012275:Oryza / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D030821:Plants, Genetically Modified; D011401:Promoter Regions, Genetic / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D011994:Recombinant Proteins; D012639:Seeds / Q000378:metabolism* / Q000648:ultrastructure; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor