Matrix metalloproteinase-9 (gelatinase B) is elevated during mobilization of peripheral blood progenitor cells by G-CSF.
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.


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.
Carstanjen
Dirk
D
Charité, University Hospital, Blood Bank, Berlin, Germany.
Ulbricht
Norbert
N
Iacone
Antonio
A
Regenfus
Michael
M
Salama
Abdulgabar
A
D002478:Cells, Cultured / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D004792:Enzyme Precursors / Q000096:biosynthesis / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D016209:Interleukin-8 / Q000502:physiology; D007937:Leukapheresis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics
D004792:Enzyme Precursors; D015850:Interleukin-6; D016209:Interleukin-8; D019010:Vascular Cell Adhesion Molecule-1; D016179:Granulocyte Colony-Stimulating Factor; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9