Metalloproteinase-7 contributes to joint destruction in Staphylococcus aureus induced arthritis
Metalloproteinase-7 contributes to joint destruction in Staphylococcus aureus induced arthritis
复制标题
DOI：
10.1016/j.micpath.2004.12.005
复制
发表时间：
2005-02-01
影响因子：
3.8
通讯作者：
Tarkowski, A
中科院分区：
文献类型：
--
作者：
Gjertsson, I;Innocenti, M;Tarkowski, A
由金黄色葡萄球菌引起的脓毒性关节炎导致关节软骨和关节周围骨的快速破坏。这种现象背后的机制尚未完全了解。早期研究表明，细胞因子和金属蛋白酶在骨代谢中起重要作用。基质金属蛋白酶-7（MMP-7）具有多种功能，包括促进巨噬细胞和中性粒细胞的迁移。本研究的目的是探讨MMP-7表达在脓毒性关节炎中的意义。MMP-7缺陷小鼠和同源对照小鼠静脉接种致关节炎剂量的S.金黄色葡萄球菌LS-1。这项研究表明，MMP-7缺陷小鼠暴露于S。金黄色葡萄球菌在临床上和组织学上都发展出明显不那么严重的关节炎。尽管有这一发现，缺陷动物中的细菌生长显著增加。MMP-7（+/+）和MMP-7（-/-）小鼠对葡萄球菌抗原和超抗原的体外反应在细胞因子产生方面没有差异，如果有的话，某些趋化因子的产生增加。此外，MMP-7（-/）-小鼠在细菌接种前和接种后1天表现出外周血单核细胞数量减少，但在第1天外周粒细胞数量增加。总之，MMP-7有助于脓毒性关节炎的破坏性过程的发展，尽管减少细菌负荷。此外，MMP-7的表达对外周血白细胞的分布有重要意义。(c)2005爱思唯尔有限公司保留所有权利。
Septic arthritis induced by Staphylococcus aureus causes a rapid destruction of joint cartilage and periarticular bone. The mechanisms behind this phenomenon are not fully understood. Earlier studies have shown that cytokines and metalloproteinases are of importance in bone metabolism. Matrix metalloprotemase-7 (MMP-7) has pleiotropic function including facilitating migration of both macrophages and neutrophils. The aim of this study has been to investigate the significance of MMP-7 expression in septic arthritis. MMP-7 deficient mice and congeneic controls were intravenously inoculated with an arthritogenic dose of S. aureus LS-1. This study shows that MMP-7 deficient mice exposed to S. aureus developed significantly less severe arthritis both clinically and histologically. Despite this finding, bacterial growth in the deficient animals was significantly increased. In vitro responses to staphylococcal antigens and superantigens did not differ between MMP-7(+/+) and MMP-7(-/-) mice with respect to cytokine production and if anything increased the production of certain chemokines. In addition MMP-7(-/)- mice exhibited decreased numbers of peripheral blood mononuclear cells before and one day after bacterial inoculation, but increased numbers of peripheral granulocytes on day 1. In conclusion, MMP-7 contributes to the development of a destructive course of septic arthritis despite decreased bacterial load. In addition, expression of MMP-7 is of importance for the distribution of peripheral leukocytes. (c) 2005 Elsevier Ltd. All rights reserved.