BCG-INDUCED GRANULOMA-FORMATION IN MURINE TISSUES
BCG-INDUCED GRANULOMA-FORMATION IN MURINE TISSUES
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DOI：
10.1016/s0171-2985(11)80442-0
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发表时间：
1994-10-01
期刊：
影响因子：
2.8
通讯作者：
STEIN, M
中科院分区：
文献类型：
--
作者：
GORDON, S;KESHAV, S;STEIN, M
BCG感染小鼠为研究结核分枝杆菌的自然免疫和细胞免疫以及肉芽肿的形成和修复机制提供了一个方便的模型。我们已经使用了一系列的巨噬细胞（M Phi）膜分子和分泌产物来研究未成熟、正常成年和γ干扰素缺乏动物的不同组织中的常驻M Phi-病原体相互作用和T淋巴细胞依赖的M Phi募集和激活。原位杂交（ISH）、RT-PCR和免疫细胞化学分析M Phi、基因和产物表达已与体外研究相关，其中，在Th 1和Th 2细胞因子、LPS、BCG和其它刺激物暴露于明胶聚丙烯酰胺珠引发的腹膜M Phi的内吞和分泌活性中，常驻和新募集的M Phi对BCG在肝、脾、肺和脑的免疫缺陷通过由MPhi（F4/80、7/4、CR 3、巨唾液酸蛋白、唾液酸粘附素和清道夫受体）和/或T和B淋巴样细胞（MHC II类、CD 4、CD 8、B220）表达的抗原标志物来定义。通过溶菌酶、TNF-α、IL-1、IL-6和MCP-1的ISH分析，通过体外测定NO和超氧阴离子产生，以及通过组织中Th 1（干扰素γ）和Th 2（IL-4、IL-13、IL-10）淋巴因子mRNA的RT-PCR研究，揭示了异源胞浆菌中的分泌活性。我们的研究证实了干扰素γ作为宿主抵抗分枝杆菌感染的关键介质的重要性，并提出了关于T细胞和M Phi功能异质性在不同组织微环境中的有趣问题。
BCG infection of mice provides a convenient model to study natural and cellular immunity to mycobacteria and the mechanisms of granuloma formation and repair. We have used a range of macrophage (M Phi membrane molecules and secretory products to investigate resident M Phi-pathogen interactions and T lymphocyte-dependent recruitment and activation of M Phi in different tissues of immature, normal adult and gamma interferon deficient animals. In situ hybridization (ISH), RT-PCR and immunocytochemical analysis of M Phi, gene and product expression have been correlated with in vitro study of endocytic and secretory activity in which biogel polyacrylamide bead-elicited peritoneal M Phi, are exposed to Th1 and Th2 cytokines, LPS, BCG and other stimuli.The role of resident and newly recruited M Phi responding to BCG in liver, spleen, lung and brain has been defined by means of antigen markers expressed by M Phi (F4/80, 7/4, CR3, macrosialin, sialoadhesin and scavenger receptor) and/or T and B lymphoid cells (MHC Class II, CD4, CD8, B220). Heterogeneity in M Phi, secretory activity was revealed by ISH analysis of lysozyme, TNF-alpha, IL-1 IL-6 and MCP-1, by in vitro assay of NO and superoxide anion production, and by RT-PCR studies of Th1 (interferon gamma) and Th2 (IL-4, IL-I3, IL-10) lymphokine mRNA in tissues. Our studies confirm the importance of interferon gamma as a critical mediator of host resistance to mycobacterial infection and raise intriguing questions in regard to T cell and M Phi functional heterogeneity in distinct tissue microenvironments.