Novel roles of osteopontin and CXC chemokine ligand 7 in the defence against mycobacterial infection
Novel roles of osteopontin and CXC chemokine ligand 7 in the defence against mycobacterial infection
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DOI：
10.1111/j.1365-2249.2005.02985.x
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发表时间：
2006-02-01
影响因子：
4.6
通讯作者：
Hara, T
中科院分区：
文献类型：
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作者：
Khajoee, V;Saito, M;Hara, T
粒细胞-巨噬细胞集落刺激因子(GM-CSF)诱导的人单核细胞来源的巨噬细胞(GM-M Phi)和巨噬细胞脑脊液(M-CSF)诱导的人单核细胞来源的M Phi(M-M Phi)对结核分枝杆菌的耐药性不同。为了阐明参与这些Phi S之间功能差异的分子所起的作用，我们利用基因芯片研究了这些基因的表达谱。巨噬细胞集落刺激因子与CD14(+)单核细胞共培养后，加入或不加入卡介苗(GM-M-Phi-BCG和M-M-Phi-BCG)培养M Phi-S。比较这些细胞的基因表达谱。选择在M-M phi S中高表达的趋化因子，并对其抗分枝杆菌活性和超氧化物歧化产物进行评价。FN1和FCGR2B分别是GM-MPhi和M-MPhi中上调最多的基因。经卡介苗刺激后，3种趋化因子基因(骨桥蛋白(SPP1)、CXC趋化因子配体7(CXCL7)和CC趋化因子配体11(CCL11))在M-M Phi-BCG中较GM-M Phi-BCG高表达。SPP1或CXCL7刺激GM-M Phi后，对结核分枝杆菌H37Ra的耐药性显著增加。SPP_1或CXCL_7刺激的GM-M Phi S细胞的超氧阴离子产生水平高于未刺激的GM-M Phi S组。这些结果表明，SPP1和CXCL7在分枝杆菌对分枝杆菌的抗性中可能都有作用，至少部分是通过增加M phi S体内活性氧中间产物的产生来实现的。
Granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced human monocyte-derived macrophage (GM-M phi) or macrophage CSF (M-CSF)-induced human monocyte-derived M phi (M-M phi) are distinct in terms of the resistance to Mycobacterium tuberculosis. To elucidate the role of molecules involved in the functional differences between these M phi s, we investigated the gene expression profiles using microarray. After culture of CD14(+) monocytes with CSFs, M phi s were cultured with or without bacillus Calmette-Guerin (BCG) (GM-M phi-BCG and M-M phi-BCG). The gene expression profiles from these cells were compared. Chemokines highly expressed in M-M phi s were selected and evaluated for anti-mycobacterial activity and superoxide production. FN1 and FCGR2B were the most up-regulated genes in GM-M phi and M-M phi, respectively. After stimulation with BCG, three chemokine genes (Osteopontin (SPP1), CXC chemokine ligand 7 (CXCL7) and CC chemokine ligand 11 (CCL11)) were highly expressed in M-M phi-BCG when compared to those in GM-M phi-BCG. A significantly increased resistance to M. tuberculosis H37Ra was observed after the stimulation of GM-M phi with SPP1 or CXCL7. Superoxide production levels of SPP1- or CXCL7-stimulated GM-M phi s were higher than those of GM-M phi s without stimulation. These results indicate that both SPP1 and CXCL7 might have a role in the resistance against mycobacteria, at least in part, through augmenting reactive oxygen intermediate production in M phi s.