Guo Na, Zhang Kui, Lv Minghua, Miao Jinlin, Chen Zhinan, Zhu Ping
Department of Cell Biology, Fourth Military Medical University, Xi'an, Shaanxi Province, China; Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Mol Immunol. 2015 Feb;63(2):253-63. doi: 10.1016/j.molimm.2014.07.005. Epub 2014 Aug 1.
Homotypic cell aggregation plays important roles in physiological and pathological processes, including embryogenesis, immune responses, angiogenesis, tumor cell invasion and metastasis. CD147 has been implicated in most of these phenomena, and it was identified as a T cell activation-associated antigen due to its obvious up-regulation in activated T cells. However, the explicit function and mechanism of CD147 in T cells have not been fully elucidated. In this study, large and compact aggregates were observed in Jurkat T cells after treatment with the specific CD147 monoclonal antibody HAb18 or after the expression of CD147 was silenced by RNA interference, which indicated an inhibitory effect of CD147 in T cell homotypic aggregation. Knocking down CD147 expression resulted in a significant decrease in CD98, along with prominent cell aggregation, similar to that treated by CD98 and CD147 monoclonal antibodies. Furthermore, decreased cell chemotactic activity was observed following CD147- and CD98-mediated cell aggregation, and increased aggregation was correlated with a decrease in the chemotactic ability of the Jurkat T cells, suggesting that CD147- and CD98-mediated homotypic cell aggregation plays a negative role in T cell chemotaxis. Our data also showed that p-ERK, p-ZAP70, p-CD3ζ and p-LCK were significantly decreased in the CD147- and CD98-knocked down Jurkat T cells, which suggested that decreased CD147- and/or CD98-induced homotypic T cell aggregation and aggregation-inhibited chemotaxis might be associated with these signaling pathways. A role for CD147 in cell aggregation and chemotaxis was further indicated in primary CD4(+) T cells. Similarly, low expression of CD147 in primary T cells induced prominent cell aggregation and this aggregation attenuated primary T cell chemotactic ability in response to CypA. Our results have demonstrated the correlation between homotypic cell aggregation and the chemotactic response of T cells to CypA, and these data indicate that CD147 and CD98 might play important roles in cyclophilin-induced cell migration.
同型细胞聚集在生理和病理过程中发挥着重要作用，包括胚胎发育、免疫反应、血管生成、肿瘤细胞侵袭和转移。CD147与这些现象中的大多数都有关联，并且由于其在活化T细胞中明显上调而被鉴定为T细胞活化相关抗原。然而，CD147在T细胞中的具体功能和机制尚未完全阐明。在本研究中，用特异性CD147单克隆抗体HAb18处理Jurkat T细胞后或通过RNA干扰使CD147表达沉默后，观察到形成了大而紧密的聚集体，这表明CD147对T细胞同型聚集具有抑制作用。敲低CD147表达导致CD98显著减少，同时细胞聚集明显，类似于用CD98和CD147单克隆抗体处理后的情况。此外，在CD147和CD98介导的细胞聚集后观察到细胞趋化活性降低，并且聚集增加与Jurkat T细胞趋化能力降低相关，这表明CD147和CD98介导的同型细胞聚集在T细胞趋化中起负作用。我们的数据还表明，在敲低CD147和CD98的Jurkat T细胞中，p-ERK、p-ZAP70、p-CD3ζ和p-LCK显著降低，这表明CD147和/或CD98诱导的同型T细胞聚集减少以及聚集抑制的趋化作用可能与这些信号通路有关。在原代CD4(+) T细胞中进一步表明了CD147在细胞聚集和趋化中的作用。同样，原代T细胞中CD147的低表达诱导了明显的细胞聚集，并且这种聚集减弱了原代T细胞对环孢素A的趋化能力。我们的结果证明了同型细胞聚集与T细胞对环孢素A的趋化反应之间的相关性，并且这些数据表明CD147和CD98可能在亲环素诱导的细胞迁移中起重要作用。
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