Effects of anti-GR-1 antibody treatment on blood and marrow PMNs and CFU-GM mobilization by GROβ proteins and G-CSF
. | PMN × 106/mL blood (% PMNs)*† . | . | INCs/femur × 106*†‡ . | . | Segmented neutrophils/femur × 106*† . | . | Fold increase CFU-GM/mL blood* . | . | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mobilizer . | Isotype . | Anti-GR-1 . | Isotype . | Anti-GR-1 . | Isotype . | Anti-GR-1 . | Isotype . | Anti-GR-1 . | ||||
| PBS | 1.3 ± 0.2 (16 ± 1.6) | 0.06 ± .04 (0.6 ± 0.3)§ | 2.89 ± 0.13 | 1.07 ± 0.08§ | 1.80 ± 0.1 | 0.05 ± 0.02§ | 1.0 ± 0.1 | 1.0 ± 0.1 | ||||
| GROβ | 1.0 ± 0.1 (15 ± 0.9) | 0.01 ± .01 (0.4 ± 0.2)§ | 2.62 ± 0.11 | 0.90 ± 0.06§ | 1.74 ± 0.1 | 0.08 ± 0.02§ | 24.7 ± 7.2∥ | 0.8 ± 0.1§ | ||||
| GROβT (SB251353) | 1.1 ± 0.7 (14 ± 1.1) | 0.01 ± .02 (0.4 ± 0.3)§ | 2.71 ± 0.21 | 0.63 ± 0.08§ | 1.81 ± 0.3 | 0.06 ± 0.05§ | 26.8 ± 8.4∥ | 0.6 ± 0.2§ | ||||
| G-CSF | 2.9 ± 0.3 (32 ± 1.5)* | 0.04 ± .03 (1.1 ± 0.6)§ | 5.75 ± 0.10§ | 0.87 ± 0.02§ | 3.42 ± 0.2§ | 0.44 ± 0.03§ | 18.5 ± 2.1∥ | 1.4 ± 0.2§ | ||||
| G-CSF + GROβ | 6.7 ± 0.4 (61 ± 3.8)* | 0.02 ± .01 (0.8 ± 0.3)§ | 4.32 ± 0.09§ | 0.91 ± 0.04§ | 1.34 ± 0.1§ | 0.31 ± 0.01§ | 135.2 ± 9.2∥ | 1.8 ± 0.3§ | ||||
| G-CSF + GROβT | 6.9 ± 0.5 (64 ± 3.3)* | 0.01 ± .01 (0.7 ± 0.2)§ | 4.19 ± 0.09§ | 0.86 ± 0.04§ | 1.29 ± 0.2§ | 0.27 ± 0.03§ | 146.7 ± 12.2∥ | 1.6 ± 0.4§ | ||||
. | PMN × 106/mL blood (% PMNs)*† . | . | INCs/femur × 106*†‡ . | . | Segmented neutrophils/femur × 106*† . | . | Fold increase CFU-GM/mL blood* . | . | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mobilizer . | Isotype . | Anti-GR-1 . | Isotype . | Anti-GR-1 . | Isotype . | Anti-GR-1 . | Isotype . | Anti-GR-1 . | ||||
| PBS | 1.3 ± 0.2 (16 ± 1.6) | 0.06 ± .04 (0.6 ± 0.3)§ | 2.89 ± 0.13 | 1.07 ± 0.08§ | 1.80 ± 0.1 | 0.05 ± 0.02§ | 1.0 ± 0.1 | 1.0 ± 0.1 | ||||
| GROβ | 1.0 ± 0.1 (15 ± 0.9) | 0.01 ± .01 (0.4 ± 0.2)§ | 2.62 ± 0.11 | 0.90 ± 0.06§ | 1.74 ± 0.1 | 0.08 ± 0.02§ | 24.7 ± 7.2∥ | 0.8 ± 0.1§ | ||||
| GROβT (SB251353) | 1.1 ± 0.7 (14 ± 1.1) | 0.01 ± .02 (0.4 ± 0.3)§ | 2.71 ± 0.21 | 0.63 ± 0.08§ | 1.81 ± 0.3 | 0.06 ± 0.05§ | 26.8 ± 8.4∥ | 0.6 ± 0.2§ | ||||
| G-CSF | 2.9 ± 0.3 (32 ± 1.5)* | 0.04 ± .03 (1.1 ± 0.6)§ | 5.75 ± 0.10§ | 0.87 ± 0.02§ | 3.42 ± 0.2§ | 0.44 ± 0.03§ | 18.5 ± 2.1∥ | 1.4 ± 0.2§ | ||||
| G-CSF + GROβ | 6.7 ± 0.4 (61 ± 3.8)* | 0.02 ± .01 (0.8 ± 0.3)§ | 4.32 ± 0.09§ | 0.91 ± 0.04§ | 1.34 ± 0.1§ | 0.31 ± 0.01§ | 135.2 ± 9.2∥ | 1.8 ± 0.3§ | ||||
| G-CSF + GROβT | 6.9 ± 0.5 (64 ± 3.3)* | 0.01 ± .01 (0.7 ± 0.2)§ | 4.19 ± 0.09§ | 0.86 ± 0.04§ | 1.29 ± 0.2§ | 0.27 ± 0.03§ | 146.7 ± 12.2∥ | 1.6 ± 0.4§ | ||||
Mice received 150 μg/mouse monoclonal anti-GR-1, clone RB6-8C5, or rat IgG2b isotype control mAb before mobilization. Antibodies were administered 4 days before GROβ/GROβT administration. For G-CSF or G-CSF plus GROβ/GROβT mobilization studies, mice received anti-GR-1 or control mAb prior to the first dose of G-CSF and again midway through the G-CSF dosing regimen. All cell counts and CFU-GM assays were performed 96 hours after anti-GR-1 administration.
Data from 4 experiments; 3 mice/experiment.
Manual differentials (200 cells/slide) were performed on Wright-Geimsa—stained blood smears and cytospins from each animal.
Immature neutrophilic cells: myeloblasts, promyelocytes, metamyelocytes, and ring and band neutrophils.
P < .001.
P < .005.