[Radioprotection of recombinant human interleukin-3 and granulocyte-macrophage colony-stimulating factor on peripheral lymphocytes of rhesus monkey irradiated by 3.0 Gy gamma-rays].
OBJECTIVE
To observe the radioprotection of recombinant human interleukin-3 (rhIL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and rhIL-3 (rhIL-3+GM-CSF) on peripheral lymphocytes of rhesus monkey irradiated by 3.0 Gy gamma-rays, and attempt to provide evidence of cytokines used effectively in the therapy of acute radiation sickness.


METHODS
Thirty rhesus monkey used in the experiment were randomly divided into six groups of rhIL-3 20 microg.kg -1.d -1, 60 microg.kg -1.d -1 GM-CSF 10 microg.kg -1.d -1 IL-3 20 microg.kg -1.d -1 +GM-CSF 10 microg.kg -1.d -1 radiation control and normal control. 21 d after whole body gamma-irradiation and subcutaneous injection of cytokines, T lymphocyte and its subsets, Bax/Bcl-2 proteins in lymphocytes were determined by immunohistochemical staining with alkaline phosphatase, and lymphocyte apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL) technique.


RESULTS
(1) After irradiation the quantities of peripheral lymphocyte, T cell and its subsets obviously decreased as compared with those of normal controls. For instance, the percentages of lymphocyte, T, T H and Ts cells in radiation control group reduced to 44 percent, 42 percent, 41 percent and 57 percent of normal controls, respectively. (2)After radiation the reduction of lymphocyte, T, T H and Ts cells were evidently improved by injection of GM-CSF and GM-CSF+IL-3, The T,T H cells in GM-CSF and GM-CSF+IL-3 groups were respectively elevated by 1.57 and 1.76 fold, as well as 1.48 and 1.72 fold of radiation controls. (3) A large amount of lymphocyte apoptosis was found after radiation, GM-CSF and GM-CSF+IL-3 treatment could distinctively inhibit abundant lymphocyte apoptosis induced by acute irradiation,the apoptotic rates of lymphocytes in GM-CSF and GM-CSF+IL-3 groups reduced to 41 percent and 48 percent respectively when compared with that of radiation controls.


CONCLUSIONS
A definite dose of GM-CSF and GM-CSF+IL-3 could suppress the reduction of lymphocyte, T and T H cells and lymphocyte apoptosis induced by 3.0 Gy gamma-irradiation. It confirms that inhibition of GM-CSF and GM-CSF+IL-3 on lymphocyte reduction as well as apoptosis might be one of the major causes to alleviate radiation injury of lymphocytes and improve the immunological function.
Cui
Yu-fang
YF
Beijing Institute of Radiation Medicine, Military Academy Medical Sciences, Beijing 100850, China.
Yang
Hong
H
Luo
Qing-liang
QL
Dong
Bo
B
Liu
Xiao-lan
XL
Xu
Han
H
Mao
Bing-zhi
BZ
Wang
De-wen
DW
D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007377:Interleukin-3 / Q000494:pharmacology*; D008214:Lymphocytes / Q000737:chemistry / Q000187:drug effects* / Q000528:radiation effects*; D008253:Macaca mulatta; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011897:Random Allocation; D011994:Recombinant Proteins / Q000494:pharmacology; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000469:Alkaline Phosphatase