Study on mechanisms of metalloproteinase release from human eosinophils

近年来，各种细胞的蛋白酶可能参与炎症性疾病和恶性疾病的细胞侵袭、组织损伤和组织重塑。同样在支气管哮喘中，来自白细胞的蛋白酶，特别是基质金属蛋白酶-9 (MMP-9)，可能会导致细胞外基质和基底膜的破坏，从而导致气道重塑。然而，目前尚不清楚MMP-9是通过什么刺激或如何从组织中的白细胞（包括嗜酸性粒细胞）中释放的。1999年，我们主要研究了人类中性粒细胞在各种刺激下释放的MMP-9。结果如下：在来自人白细胞的单核细胞、中性粒细胞和嗜酸性粒细胞的三个组分中，中性粒细胞释放的MMP-9最多。在C5a、FMLP和PAF作为中性粒细胞的基质中，FMLP诱导MMP-9的释放量最大。FMLP的刺激作用在10^<-8>M时达到最大。GM-CSF预孵育可增强fmlp诱导的MMP-9释放。在2000年，我们检测了在不同条件下人嗜酸性粒细胞释放MMP-9，并检测了人中性粒细胞释放MMP-9的信号转导。结果如下：无论是否有IL-5启动，人嗜酸性粒细胞对C5a、FMLP或PAF均不释放大量的MMP-9。其次，百日咳毒素（PTX）预处理明显抑制fmlp诱导的MMP-9从人中性粒细胞释放。因此，我们认为ptx敏感的G蛋白可能参与了fmlp诱导的MMP-9释放的信号转导。综上所述，MMP-9主要由人白细胞中的中性粒细胞释放，FMLP最有效地诱导MMP-9释放，其中ptx敏感的G蛋白可能参与了信号转导。

Recently it has been suggested that proteinase from various cells may be involved in cell invasion, tissue damage and tissue remodelling in inflammatory diseases and malignant diseases. Also in bronchial asthma, there is a possibility that proteinase from leukocytes, especially matrix metalloproteinase-9 (MMP-9), induces disruption of extracellular matrix and basement membranes leading to airway remodelling. However, it is unclear by what stimulus or how MMP-9 is released from leukocytes including eosinophils in tissue.In 1999, we mainly examined MMP-9 release from human neutrophils in response to various stimuli. The results were as follows. Among three fractions of mononuclear cells, neutrophils and eosinophils from human leukocytes, neutrophils released the largest amount of MMP-9. Among C5a, FMLP and PAF as stumuli for neutrophils, FMLP induced the release of the largest amount of MMP-9. The stimulus effect of FMLP was maximal at 10^<-8>M.Preincubation with GM-CSF enhanced FMLP-induced MMP-9 release.In 2000, we examined MMP-9 release from human eosinophils under various conditions, and also examined signal transduction in MMP-9 release from human neutrophils. The results were as follows. Human eosinophils did not release significant amount of MMP-9 in response to C5a, FMLP or PAF either without or with IL-5 priming. Next, pertussis toxin (PTX) pretreatment clearly inhibited FMLP-induced MMP-9 release from human neutrophils. Therefore, it was suggested that PTX-sensitive G protein may be involved in signal transduction in FMLP-induced MMP-9 release. In summary, it was indicated that MMP-9 is mostly released from neutrophils among human leukocytes and that FMLP most effectively induces MMP-9 release, in which PTX-sensitive G protein may be involved in signal transduction.