期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 39, 期 12, 页码 3538-3551出版社
WILEY
DOI: 10.1002/eji.200939530
关键词
BM; Gr-1; Macrophages; Myelopoiesis; Myeloid-derived suppressor cells
类别
资金
- Deutsche Forschungsgemeinschaft (DFG) [DFG LU851/4-1]
- Collaborative Research Center [SFB 479]
- Institute of Virology and Immunobiology in Wurzburg
The Gr-1 (RB6-8C5) Ab binds with high affinity to mouse Ly-6G molecules and to a lower extent to Ly-6C and has been widely used for cell depletion in infected or tumor-bearing mice. Here we found that Gr-1 treatment of BM cells in vitro and in vivo showed no depleting effects. The epitope recognized by the Gr-1 Ab overlapped with Ly-6G (1A8 Ab) but not Ly-6C (ER-MP20 Ab). in vitro the Gr-1 Ab transmitted signals via STAT-1, STAT-3 and STAT-5 into BM cells, similar to GM-CSF. In healthy mice injected with the Gr-1 Ab, the Ab remained attached to the surface of myeloid cells for at least four days. Gr-1 Ab induced myeloid cell expansion, upregulation of macrophage markers, but not the DC marker CD11c. Suppressor activity of two distinct Gr-1(high) and Gr-1(low) expressing BM-myeloid-derived suppressor cell subsets was transiently ablated by Gr-1 Ab injection. Depleting effects of Gr-1 Ab could only be observed on inflammatory Ly-6C(int)Ly-6G(high) neutrophils from the peritoneal cavity, which occurred via apoptosis and was associated with the absence of Mcl-1 expression. Together, Gr-1 Ab induces signals leading to myelopoiesis and affects myeloid-derived suppressor cell activity, suggesting functional roles for Ly-6C/G molecules in macrophage differentiation and neutrophil apoptosis.
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