Differential expression of three T lymphocyte-activating CXC chemokines by human atheroma-associated cells
Differential expression of three T lymphocyte-activating CXC chemokines by human atheroma-associated cells
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DOI：
10.1172/jci6993
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发表时间：
1999-10-01
影响因子：
15.9
通讯作者：
Luster, AD
中科院分区：
文献类型：
--
作者：
Mach, F;Sauty, A;Luster, AD
活化的T淋巴细胞在动脉粥样硬化形成的早期积累，并持续存在于病变生长和破裂的部位，这表明它们可能在动脉粥样硬化的发病机制中起重要作用。此外，动脉粥样硬化病变含有Th 1型细胞因子IFN-γ，动脉粥样硬化的增强剂。本研究证实了3种IFN-γ诱导的CXC趋化因子-IFN-诱导蛋白10（IP-10）、IFN-γ诱导的单核因子（Mig）和IFN-诱导的T细胞α趋化因子（T-TAC）-通过动脉粥样硬化相关细胞的差异表达，以及它们的受体CXCR 3通过人原位动脉粥样硬化病变内的所有T淋巴细胞的表达。免疫荧光双标法显示，动脉粥样硬化相关内皮细胞（EC）、平滑肌细胞（SMCs）和巨噬细胞（M phi）均表达IP-10，而Mig和I-TAC主要表达于EC和M phi。病变内微血管内皮细胞也表达丰富的I-TAC。体外实验支持这些结果，并显示IL-1 β、TNF-α和CD 40配体增强IFN-γ刺激的EC的IP-10表达。此外，一氧化氮（NO）治疗减少IFN-γ诱导IP-10。我们的研究结果表明，IP-10，米格，和I-TAG的动脉粥样硬化相关细胞的差异表达起着一定的作用，在招募和保留的活化T淋巴细胞观察血管壁病变在动脉粥样硬化形成。
Activated T lymphocytes accumulate early in atheroma formation and persist at sites of lesion growth and rupture, suggesting that they may play an important role in the pathogenesis of atherosclerosis. Moreover, atherosclerotic lesions contain the Th1-type cytokine IFN-gamma, a potentiator of atherosclerosis. The present study demonstrates the differential expression of the 3 IFN-gamma-inducible CXC chemokines - IFN-inducible protein 10 (IP-10), monokine induced by IFN-gamma (Mig), and IFN-inducible T-cell a chemoattractant (T-TAC) - by atheroma-associated cells, as well as the expression of their receptor, CXCR3, by all T lymphocytes within human atherosclerotic lesions in situ. Atheroma-associated endothelial cells (ECs), smooth muscle cells (SMCs), and macrophages (M phi) all expressed IP-10, whereas Mig and I-TAC were mainly expressed in ECs and M phi, as detected by double immunofluorescence staining. ECs of microvessels within lesions also expressed abundant I-TAC. In vitro experiments supported these results and showed that IL-1 beta, TNF-alpha and CD40 ligand potentiated IP-10 expression from IFN-gamma-stimulated ECs. In addition, nitric oxide (NO) treatment decreased IFN-gamma induction of IP-10. Our findings suggest that the differential expression of IP-10, Mig, and I-TAG by atheroma-associated cells plays a role in the recruitment and retention of activated T lymphocytes observed within vascular wall lesions during atherogenesis.