Mechanistic insights for chemokine/cytokine-induced mobilization
Mobilizing regimen . | Reference . | Associated findings . | Proposed mechanisms . | Comments . |
|---|---|---|---|---|
| IL-8 | 10,20 | ↑ in MMP-9 | MMP-9-dependent; PMNs are target cells | Anti-PMN Abs or anti-MMP-9 abrogates the effect |
| Groβ | 6,21,27 | ↑ in MMP-9 | MMP-9-dependent; PMNs are target cells | Attenuated response in MMP-9-/- mice; anti-PMN Ab abrogates the effect |
| SDF-1 (adeno SDF-1) | 9 | ↑ SDF-1 in PB | Reversal of BM to PB SDF-1 gradient (?) | MMP-9-/- mice do not respond. No accumulation of cells in liver, the site of production of SDF-1.22 |
| Met SDF-1 | 23 | NA | Noncleavable SDF-1→Desensitization of CXCR4 | No phenotypic/functional studies of mobilized cells |
| AMD-3100 (CXCR4 antagonist) | 24 | NA | Down-regulation of CXCR4: abrogation of signaling | No phenotypic/functional studies of mobilized cells |
| VEGF (adeno VEGF) | 9 | ↑ MMP-9, ↑ SDF-1 in PB | Mostly MMP-9-dependent | No response in MMP-9-/- mice. No response in Id1/Id3-deficient mice.25 |
| Ang-1 (adeno Ang-1) | 9 | NA | HPCs not a direct target | Delayed response in WT mice |
| G-CSF | 4,7 | BM: ↑ NE, ↑ CG, ↓ SDF-1. PB: ↑ MMP-9 | Proteolytic degradation of important target molecules in BM: SDF-1, CXCR4, VCAM-1, kit, (G-CSF), other? | Protease-deficient mice have an unimpaired response to G-CSF, but show ↓ SDF-1 in BM.18 No change in BM to PB SDF-1 gradient.26 |
Mobilizing regimen . | Reference . | Associated findings . | Proposed mechanisms . | Comments . |
|---|---|---|---|---|
| IL-8 | 10,20 | ↑ in MMP-9 | MMP-9-dependent; PMNs are target cells | Anti-PMN Abs or anti-MMP-9 abrogates the effect |
| Groβ | 6,21,27 | ↑ in MMP-9 | MMP-9-dependent; PMNs are target cells | Attenuated response in MMP-9-/- mice; anti-PMN Ab abrogates the effect |
| SDF-1 (adeno SDF-1) | 9 | ↑ SDF-1 in PB | Reversal of BM to PB SDF-1 gradient (?) | MMP-9-/- mice do not respond. No accumulation of cells in liver, the site of production of SDF-1.22 |
| Met SDF-1 | 23 | NA | Noncleavable SDF-1→Desensitization of CXCR4 | No phenotypic/functional studies of mobilized cells |
| AMD-3100 (CXCR4 antagonist) | 24 | NA | Down-regulation of CXCR4: abrogation of signaling | No phenotypic/functional studies of mobilized cells |
| VEGF (adeno VEGF) | 9 | ↑ MMP-9, ↑ SDF-1 in PB | Mostly MMP-9-dependent | No response in MMP-9-/- mice. No response in Id1/Id3-deficient mice.25 |
| Ang-1 (adeno Ang-1) | 9 | NA | HPCs not a direct target | Delayed response in WT mice |
| G-CSF | 4,7 | BM: ↑ NE, ↑ CG, ↓ SDF-1. PB: ↑ MMP-9 | Proteolytic degradation of important target molecules in BM: SDF-1, CXCR4, VCAM-1, kit, (G-CSF), other? | Protease-deficient mice have an unimpaired response to G-CSF, but show ↓ SDF-1 in BM.18 No change in BM to PB SDF-1 gradient.26 |
PMN indicates polymorphonuclear leukocyte; Ab, antibody; NA, not available; VEGF, vascular endothelial growth factor; WT, wild type; Ang-1, angiopoietin-1; HPCs, hematopoietic progenitor cells; and NE, neutrophil elastase.