Matrix metalloproteinase-9 (gelatinase B) is elevated during mobilization of peripheral blood progenitor cells by G-CSF
Matrix metalloproteinase-9 (gelatinase B) is elevated during mobilization of peripheral blood progenitor cells by G-CSF
复制标题
DOI：
10.1046/j.1537-2995.2002.00088.x
复制
发表时间：
2002-05-01
期刊：
影响因子：
2.9
通讯作者：
Salama, A
中科院分区：
文献类型：
--
作者：
Carstanjen, D;Ulbricht, N;Salama, A
背景：基质金属蛋白酶-9 （MMP-9或明胶酶B）最近在恒河猴和小鼠中与il -8诱导的HPCs动员有关。目前尚不清楚G-CSF是否会导致HPC动员过程中MMP-9的表达。研究设计和方法：在g - csf诱导的HPC动员之前和期间收集15个异体祖细胞供体的血液样本。采用酶联免疫吸附法（ELISA）和酶谱法检测供体血浆中明胶酶MMP-2和MMP-9的表达。明胶溶解活性用荧光测定法测定，该测定法对明胶酶具有特异性。ELISA法检测IL-6、IL-8和可溶性血管细胞粘附分子（VCAM）的表达。结果：与预处理活性相比，G-CSF治疗第4天和第5天的潜在明胶溶解活性显著升高。ELISA和酶谱分析显示，mmp -9是动员过程中潜在明胶溶解血浆活性的主要来源。与预处理水平相比，Pro-MMP-2未升高。由于IL-8与MMP-9的表达有关，因此在HPC采血开始前立即测量了供者和患者血浆样本中的IL-8浓度，但未注意到IL-8浓度显著升高。相比之下，mmp -9和潜在的明胶溶解活性与IL-6高度相关，IL-6在动员治疗期间显著升高。最后，可溶性VCAM在分离日同样显著升高。结论：G-CSF动员处理诱导MMP-9、IL-6和可溶性VCAM。MMP-9的表达可能参与了人类HPCs的动员，可能是不同动员疗法的最终共同途径。我们的数据不支持IL-8在g - csf诱导的动员中的作用。相反，IL-6可能参与了g - csf诱导的MMP-9的表达。
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.