The characterization of multinucleated giant cells in granulomatous inflammation

长期以来，多核巨细胞一直被认为是肺结核、血吸虫病、结节病、异物反应和其他肉芽肿性疾病的慢性肉芽肿反应的特征。它们起源于巨噬细胞的融合，并可在体外通过巨噬细胞暴露于细胞因子白介素4而产生。尽管多核巨细胞是肉芽肿反应的标志，但它们的功能意义目前尚不清楚。为了更好地了解多核巨细胞的功能及其对疾病预后的潜在贡献，我们正在使用体内和体外的方法。我们正在研究曼氏血吸虫寄生虫在缺乏巨噬细胞融合机制已知组件的小鼠身上诱导的肉芽肿性反应。此外，我们在肉芽肿的背景下以及在培养中使用mRNA表达谱和功能分析对多核巨细胞进行了全面的表型和功能分析。

Multinucleated giant cells have long been recognized as a characteristic feature of chronic granulomatous responses occurring in tuberculosis, schistosomiasis, sarcoidosis, the foreign body reaction and other granulomatous diseases. They originate from fusion of macrophages and can be generated in vitro by exposure of macrophages to the cytokine interleukin-4. Even though multinucleated giant cells are a hallmark in granulomatous responses, their functional significance is currently unknown. In order to obtain a better understanding of the function of multinucleated giant cells and their potential contribution to disease outcome, we are using in vivo and in vitro approaches. We are investigating granulomatous responses induced by the parasite Schistosoma mansoni in mice deficient in known components of the macrophage fusion machinery. In addition, we are performing a comprehensive phenotypic and functional analysis of multinucleated giant cells in the context of granulomas as well as in culture using mRNA expression profiling and functional assays.