Matrix metalloproteinase-9 (gelatinase B) is elevated during mobilization of peripheral blood progenitor cells by G-CSF
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Published on: November 28, 2015
Dirk Carstanjen1, Norbert Ulbricht, Antonio Iacone
1Charité, University Hospital, Blood Bank, Berlin, Germany.
Background:
Matrix metalloproteinase-9 (MMP-9 or gelatinase B) has recently been implicated in the IL-8-induced mobilization of HPCs in rhesus monkeys and mice. It is not known whether administration of G-CSF causes expression of MMP-9 during HPC mobilization.
Study Design And Methods:
Blood samples from 15 allogeneic progenitor cell donors were collected before and during G-CSF-induced HPC mobilization. The expression of the gelatinases MMP-2 and MMP-9 in the plasma of the donors was analyzed by ELISA and zymographic analysis. Gelatinolytic activity was measured with a fluorometric assay that was specific for gelatinases. Expression of IL-6, IL-8, and soluble vascular cell adhesion molecule (VCAM) was measured by ELISA.
Results:
Highly elevated latent gelatinolytic activity was found on Days 4 and 5 of G-CSF treatment in comparison to pretreatment activity. ELISA and zymographic analyses revealed pro-MMP-9 as the major source of the latent gelatinolytic plasma activity during mobilization. Pro-MMP-2 was not elevated compared with pretreatment levels. As IL-8 has been implicated in the expression of MMP-9, IL-8 concentrations were measured in plasma samples from donors and patients immediately before the start of HPC apheresis, but no significantly elevated IL-8 concentrations were noted. In contrast, pro-MMP-9 and latent gelatinolytic activity was highly correlated with IL-6, which was strongly elevated during mobilization therapy. Finally, soluble VCAM was equally significantly elevated on the days of apheresis.
Conclusions:
G-CSF mobilization treatment induces MMP-9, IL-6, and soluble VCAM. Expression of MMP-9 might be involved in the mobilization of human HPCs and might be a final common pathway of different mobilization therapies. Our data do not support a role of IL-8 in G-CSF-induced mobilization. In contrast, IL-6 might be involved in the G-CSF-induced expression of MMP-9.
Insights
Granulocyte-colony stimulating factor (G-CSF) treatment increases matrix metalloproteinase-9 (MMP-9) and IL-6 levels during hematopoietic progenitor cell (HPC) mobilization. These findings suggest MMP-9
Area of Science:
- Hematology
- Immunology
- Molecular Biology
Background:
- Matrix metalloproteinase-9 (MMP-9) is implicated in IL-8-induced mobilization of hematopoietic progenitor cells (HPCs).
- The role of G-CSF in inducing MMP-9 expression during HPC mobilization is unknown.
Purpose of the Study:
- To investigate whether G-CSF administration induces MMP-9 expression during HPC mobilization.
- To explore the relationship between G-CSF, MMP-9, IL-6, IL-8, and soluble VCAM during HPC mobilization.
Main Methods:
- Blood samples from 15 allogeneic HPC donors were analyzed before and during G-CSF treatment.
- ELISA and zymography were used to measure MMP-2 and MMP-9 expression and activity.
- IL-6, IL-8, and soluble VCAM levels were quantified using ELISA.
Main Results:
- G-CSF treatment significantly elevated latent gelatinolytic activity, primarily due to pro-MMP-9.
- Pro-MMP-2 levels did not increase significantly.
- Elevated pro-MMP-9 and gelatinolytic activity correlated strongly with increased IL-6, not IL-8.
- Soluble VCAM levels were also significantly elevated during apheresis.
Conclusions:
- G-CSF mobilization induces MMP-9, IL-6, and soluble VCAM expression.
- MMP-9 may play a role in human HPC mobilization, potentially as a common pathway for different mobilization therapies.
- IL-6, not IL-8, appears to be involved in G-CSF-induced MMP-9 expression.
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