Zhu Xing Wu, Friedland Jon S
Department of Infectious Diseases, Faculty of Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.
Clin Immunol. 2006 Jul;120(1):10-20. doi: 10.1016/j.clim.2006.01.009. Epub 2006 Feb 28.
Multinucleate giant cells (MGC) are characteristic of tuberculous granulomas, but their function is not well understood. In a comparative study, we investigated regulation of chemokine secretion by MGC generated using 5 microg/ml ConA and 1000 IU/ml IFN-gamma. After 72-h differentiation of MGC cultures, CXCL8, CCL2 and CCL3 concentrations were 9540+/-110 pg/ml, 11190+/-2210 pg/ml and 19440+/-440 pg/ml respectively all significantly higher than in MDM (P<0.01). There was associated increased chemokine gene expression. M.tb stimulation of MGC, MDM and monocytes increased CXCL8 secretion. M.tb increased monocyte CCL2 secretion, whereas MGC and MDM secreted CCL2 constitutively. CXCL10 secretion was induced in M.tb-stimulated MDM and constitutive in MGC. All cell types responded to M.tb with CCL3 secretion. Monocyte chemokine secretion was associated with increased gene expression, whereas M.tb-stimulated MGC principally upregulated CCL3 gene expression. In summary, differentiating MGC express genes for and secrete chemokines which regulate cell influx to sites of infection. Established MGC will contribute to cell recruitment to granuloma, but this may not depend on exposure to the pathogen.
多核巨细胞（MGC）是结核性肉芽肿的特征，但对其功能了解尚少。在一项比较研究中，我们研究了用5微克/毫升刀豆蛋白A（ConA）和1000国际单位/毫升γ干扰素（IFN-γ）产生的MGC对趋化因子分泌的调节作用。MGC培养物分化72小时后，CXCL8、CCL2和CCL3浓度分别为9540±110皮克/毫升、11190±2210皮克/毫升和19440±440皮克/毫升，均显著高于单核巨噬细胞（MDM）（P<0.01）。趋化因子基因表达也相应增加。结核分枝杆菌（M.tb）刺激MGC、MDM和单核细胞会增加CXCL8分泌。M.tb增加单核细胞CCL2分泌，而MGC和MDM组成性分泌CCL2。M.tb刺激的MDM诱导CXCL10分泌，MGC组成性分泌CXCL10。所有细胞类型对M.tb刺激均分泌CCL3。单核细胞趋化因子分泌与基因表达增加相关，而M.tb刺激的MGC主要上调CCL3基因表达。总之，分化中的MGC表达趋化因子基因并分泌趋化因子，这些趋化因子调节细胞流入感染部位。成熟的MGC有助于细胞募集到肉芽肿，但这可能不依赖于接触病原体。
