The characterization of multinucleated giant cells in granulomatous inflammation

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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.