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 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.
Ribechini
Eliana
E
Institute of Virology and Immunobiology, University of Wuerzburg, Germany.
Leenen
Pieter J M
PJ
Lutz
Manfred B
MB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology*; D000950:Antigens, Ly / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D016177:Macrophage-1 Antigen; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism; D038042:Myelopoiesis / Q000187:drug effects; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; C494192:Ly-6C antigen, mouse; C480309:Ly6G antigen, mouse; D016177:Macrophage-1 Antigen; C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D050791:STAT Transcription Factors; D016186:Receptor, Macrophage Colony-Stimulating Factor