02474nas a2200337 4500000000100000008004100001260001300042653003800055653001200093653001600105653001400121653003200135653001600167653003500183653001100218653002700229653001400256653002800270653001600298653001400314653002900328653003100357100001400388700001300402700001200415245005700427300001100484490000700495520162000502022001402122 2004 d c2004 Sep10aAcetylmuramyl-Alanyl-Isoglutamine10aAnimals10aCell Fusion10aCytokines10aFusion Regulatory Protein-110aGiant Cells10aGranulomatous Disease, Chronic10aHumans10aInflammation Mediators10aIntegrins10aLeukocytes, Mononuclear10aMacrophages10aMonocytes10aReceptors, Purinergic P210aReceptors, Purinergic P2X71 aOkamoto H1 aMizuno K1 aHorio T00a[Human monocyte-derived multinucleated giant cells]. a245-510 v733 a
Multinucleated giant cells (MGC) are characteristic cells in granulomatous disorders such as sarcoidosis and leprosy. There are two types of MGC; foreign body-type and Langhans-type cells. The exact mechanisms of the formation and the functional significance of MGC are not determined, although their morphological features are well understood. MGC are also formed in vitro from peripheral blood mononuclear cells by stimulation with cytokines and lectins. Particularly IFN-gamma is considered to play a pivotal role in monocyte fusion. IL-3, IL-4, IL-13, and GM-CSF are other reported cytokines involved in MGC formation. In addition to such inflammatory mediators, a factor derived from the pathogens of granulomatous disorders may be necessary for MGC formation. Muramyl dipeptide, a peptidoglycan portion of bacterial cell walls, is one of the candidates and can preferentially induce Langhans-type cells in in vitro MGC formation system. Although the exact mechanisms of in vitro MGC formation remains unknown, cell surface molecules such as P2X7 receptor, integrins, CD98, and macrophage fusion protein are considered to be involved in fusion process. Monocytes of sarcoidosis patients expressed higher levels of P2X7 and had a higher ability to induce MGC than those of healthy controls. Effective agents for sarcoidosis such as tranilast, alloprinol, and captopril inhibited in vitro MGC formation, suggesting their therapeutic effects through the direct effects on monocytes. Thus, an in vitro MGC formation model would be a useful tool to understand the relevance of MGC in granulomatous disorders.
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