期刊
CYTOKINE
卷 60, 期 3, 页码 793-805出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2012.08.008
关键词
Macrophage; Ba/F3 cells; Bone marrow; Hematopoiesis; Species specificity
资金
- BBSRC [338BCB R40954]
- BBSRC [BBS/E/D/20231759, BBS/E/D/20231760, BBS/E/D/20221657, BBS/E/D/20251969, BB/I013113/1] Funding Source: UKRI
- MRC [G0901193] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/I013113/1, BBS/E/D/20251969, BBS/E/D/20231759, BBS/E/D/20221657, BBS/E/D/20231760] Funding Source: researchfish
- Medical Research Council [G0901193] Funding Source: researchfish
Macrophage Colony Stimulating Factor (CSF-1) controls the survival, differentiation and proliferation of cells of the mononuclear phagocyte system. A second ligand for the CSF-1R, Interleukin 34 (IL-34), has been described, but its physiological role is not yet known. The domestic pig provides an alternative to traditional rodent models for evaluating potential therapeutic applications of CSF-1R agonists and antagonists. To enable such studies, we cloned and expressed active pig CSF-1. To provide a bioassay, pig CSF-1R was expressed in the factor-dependent Ba/F3 cell line. On this transfected cell line, recombinant porcine CSF-1 and human CSF-1 had identical activity. Mouse CSF-1 does not interact with the human CSF-1 receptor but was active on pig. By contrast, porcine CSF-1 was active on mouse, human, cat and dog cells. IL-34 was previously shown to be species-specific, with mouse and human proteins demonstrating limited cross-species activity. The pig CSF-1R was equally responsive to both mouse and human IL-34. Based upon the published crystal structures of CSF-1/CSF-1R and IL34/CSF-1R complexes, we discuss the molecular basis for the species specificity. (C) 2012 Elsevier Ltd. All rights reserved.
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