Luttikhuizen D T, Dankers P Y W, Harmsen M C, van Luyn M J A
Department of Pathology and Laboratory Medicine, Medical Biology Section, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
J Biomed Mater Res A. 2007 Dec 1;83(3):879-86. doi: 10.1002/jbm.a.31420.
Multinucleated giant cells (GCs) are often observed in the foreign body reaction against implanted materials. The in vivo function of GCs in this inflammatory process remains to be elucidated. GCs degrade collagen implants in rats and may also orchestrate the inflammatory process via the expression and secretion of modulators, such as cytokines and chemokines. In this study, we show that the gene expression of PMN chemoattractants, CXCL1/KC and CXCL2/MIP-2, is high in GCs micro-dissected from explanted Dacron, cross-linked collagen (HDSC), and bioactive ureido-pyrimidinone functionalized oligocaprolactone (bioactive PCLdiUPy). Conversely, the gene expression levels of TGFbeta and pro-angiogenic mediators VEGF and FGF were found to be low in these GCs as compared with the expression levels in total explants. GCs in bioactive PCLdiUPy displayed high cytokine and angiogenic mediator expression compared with GCs isolated from the two other studied materials, whereas chemokine gene expression in GCs isolated form HDSC was low. Thus, GCs adopt their expression profile in response to the material that is encountered.
多核巨细胞(GCs)常在针对植入材料的异物反应中被观察到。GCs在这一炎症过程中的体内功能仍有待阐明。GCs可降解大鼠体内的胶原植入物,还可能通过细胞因子和趋化因子等调节剂的表达和分泌来协调炎症过程。在本研究中,我们发现,从植入的涤纶、交联胶原(HDSC)和生物活性脲嘧啶酮功能化低聚己内酯(生物活性PCLdiUPy)中显微分离出的GCs中,中性粒细胞趋化因子CXCL1/KC和CXCL2/MIP-2的基因表达水平较高。相反,与整个植入物中的表达水平相比,在这些GCs中发现转化生长因子β(TGFbeta)以及促血管生成介质血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(FGF)的基因表达水平较低。与从其他两种研究材料中分离出的GCs相比,生物活性PCLdiUPy中的GCs表现出较高的细胞因子和血管生成介质表达,而从HDSC中分离出的GCs中的趋化因子基因表达较低。因此,GCs会根据所接触的材料来调整其表达谱。