CXCL9 and 11 in patients with pulmonary sarcoidosis: a role of alveolar macrophages
CXCL9 and 11 in patients with pulmonary sarcoidosis: a role of alveolar macrophages
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DOI：
10.1111/j.1365-2249.2007.03423.x
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发表时间：
2007-08-01
影响因子：
4.6
通讯作者：
Sone, S.
中科院分区：
文献类型：
--
作者：
Nishioka, Y.;Manabe, K.;Sone, S.
干扰素诱导蛋白-10（IP-10）/CXCL 10是CXC趋化因子受体3（CXCR 3）的配体，已知其参与肺结节病的发病机制。然而，由干扰素γ（Mig）/CXCL 9和干扰素诱导的T细胞α化学引诱物（I-TAQ/CXCL 11，它们也是CXCR 3配体）诱导的单核因子的作用仍不清楚。采用酶联免疫吸附试验（ELISA）检测肺结节病患者支气管肺泡灌洗液（BALF）和血清中Mig/CXCL 9、IP-10/CXCL 10和I-TAC/CXCL 11的表达。这些趋化因子在肺泡巨噬细胞的表达，采用ELISA，定量实时聚合酶链反应和免疫染色。BALF中Mig/CXCL 9和IP-10/CXCL 10在11期结节病中显著高于健康志愿者。在血清中，Mig/CXCL 9和I-TAC/CXCL 11在疾病的第11阶段增加。BALF中CXCR 3配体水平与总淋巴细胞数和CD 4（+）淋巴细胞数相关。肺泡巨噬细胞对所有CXCR 3配体染色呈阳性，并产生增加量的这些趋化因子。在结节病肺的上皮样细胞和巨细胞中也观察到三种趋化因子的阳性染色。提示Mig/CXCL 9、I-TAC/CXCL 11和IP-10/CXCL 10在类肉瘤肺Th 1淋巴细胞聚集中起重要作用。
Interferon-inducible protein-10 (IP-10)/CXCL10, which is a ligand for CXC chemokine receptor 3 (CXCR3), is known to be involved in the pathogenesis of pulmonary sarcoidosis. However, the roles of monokine induced by interferon gamma (Mig)/CXCL9 and interferon-inducible T cell alpha chemoattractant (I-TAQ/CXCL11, which are also CXCR3 ligands, remain unclear. Mig/ CXCL9, IP-10/CXCL10 and I-TAC/CXCL11 in both bronchoalveolar lavage fluid (BALF) and serum in patients with pulmonary sarcoidosis were measured by enzyme-linked immunosorbent assay (ELISA). The expression of these chemokines in alveolar macrophages was examined using ELISA, quantitative real-time polymerase chain reaction and immunostaining. In BALF, Mig/CXCL9 and IP-10/CXCL10 were significantly elevated in stage 11 sarcoidosis as compared with the levels in healthy volunteers. In serum, Mig/CXCL9 and I-TAC/CXCL11 were increased in stage 11 of the disease. The levels of all CXCR3 ligands in BALF were correlated with the numbers of both total and CD4(+) lymphocytes. Alveolar macrophages were stained positive for all CXCR3 ligands and produced increased amounts of these chemokines. Positive staining of the three chemokines was also observed in the epithelioid and giant cells in the sarcoid lungs. These findings suggest that Mig/CXCL9 and I-TAC/ CXCL11 as well as IP-10/CXCL10 play important roles in the accumulation of Th1 lymphocytes in sarcoid lungs.