Comparative study on primary structure and function of rhesus monkey and human granulocyte–macrophage colony stimulating factor
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1
Key Lab of Transplant Engineering and Immunology, Ministry of Health, China
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2
Regenerative Medicine Research Center, West China Hospital, Sichuan University, China
Recent studies revealed the pivotal roles of granulocyte–macrophage colony stimulating factor (GMCSF) in inflammation and arthritis, suggesting GMCSF-neutralizing agents might be developed as novel therapeutic approaches for these immune disorders. Since the rhesus monkeys Macaca mullata are usually used as animal models for pathogenesis and drug discovery for human disease, it is needed to compare the human GMCSF (hGMCSF) and M. mulatta GMCSF (mmGMCSF). Here, a 432 bp transcript encoding mmGMCSF was amplified by RT-PCR. The predicted mmGMCSF contains 144 amino acid residues with approximately 96% identity to hGMCSF. The mature mmGMCSF differs from hGMCSF at 6 amino acid residues. MmGMCSF was expressed in freshly isolated PBMCs of monkey at low level. In contrast, Con A- and allogenic antigen-stimulation significantly increased the accumulation of mmGMCSF in the media of PBMCs. Moreover, the amount of secreted mmGMCSF was consistent with the proliferation of stimulated PBMCs. These results suggested that mmGMCSF was predominantly produced by activated T cells. The recombinant mmGMCSF produced by E. coli is comparable to hGMCSF in supporting TF-1 cell growth. In the presence of human interleukin 4, mmGMCSF induced the progenitor cells in monkey PBMCs to differentiate into DCs. The hGMCSF receptor protein and the neutralizing anti-hGMCSF antibody reduced the activity of mmGMCSF in supporting TF-1 cells survival. These results suggest that the recombinant mmGMCSF might be a useful tool for in vitro evaluation of novel hGMCSF-neutralizing agents prior to in vivo evaluation in the rhesus monkey model.
Acknowledgements
This project was supported by National Program for High Technology Research and Development of China 2012AA020702 (X. Lu),and Key Program for Natural Science Fund of China 30930088 (J.Q.Cheng).
Keywords:
Granulocyte–macrophage colony stimulating factor,
autoimmune disease,
Rhesus Monkey,
Immunotherapy,
Neutralizing
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Tao
Z,
Yang
H,
Jia
D,
Wan
L,
Cheng
J and
Lu
X
(2013). Comparative study on primary structure and function of rhesus monkey and human granulocyte–macrophage colony stimulating factor.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00372
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Received:
21 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Prof. Xiaofeng Lu, Key Lab of Transplant Engineering and Immunology, Ministry of Health, Chengdu, China, xiaofenglu@yahoo.com