Gr-1 antibody induces STAT signaling, macrophage marker expression and abrogation of myeloid-derived suppressor cell activity in BM cells
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 ofmyeloid 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-1highand Gr-1lowexpressing 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-6CintLy-6Ghighneutrophils 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.
|Keywords||BM, Gr-1, Macrophages, Myeloid-derived suppressor cells, Myelopoiesis|
|Persistent URL||dx.doi.org/10.1002/eji.200939530, hdl.handle.net/1765/24085|
Ribechini, E, Leenen, P.J, & Lutz, M.B. (2009). Gr-1 antibody induces STAT signaling, macrophage marker expression and abrogation of myeloid-derived suppressor cell activity in BM cells. European Journal of Immunology, 39(12), 3538–3551. doi:10.1002/eji.200939530