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Matrix metalloproteinase‐9 (gelatinase B) is elevated during mobilization of peripheral blood progenitor cells by G–CSF
Author(s) -
Carstanjen Dirk,
Ulbricht Norbert,
Iacone Antonio,
Regenfus Michael,
Salama Abdulgabar
Publication year - 2002
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1046/j.1537-2995.2002.00088.x
Subject(s) - gelatinase , gelatinases , matrix metalloproteinase , apheresis , mobilization , progenitor cell , metalloproteinase , gelatinase a , medicine , chemistry , cell adhesion molecule , endocrinology , immunology , stem cell , biology , platelet , genetics , archaeology , history
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. CONCLUSION S: 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.