Human neutrophil gene expression profiling following xenogeneic encounter with porcine aortic endothelial cells: the occult role of neutrophils in xenograft rejection revealed
Human neutrophil gene expression profiling following xenogeneic encounter with porcine aortic endothelial cells: the occult role of neutrophils in xenograft rejection revealed
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DOI：
10.1189/jlb.0904494
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发表时间：
2005-07-01
影响因子：
5.5
通讯作者：
Collison, K
中科院分区：
文献类型：
--
作者：
Al-Mohanna, F;Saleh, S;Collison, K
在识别和激活异种内皮细胞的囚犯免疫细胞的作用一直被认为是继发于异种反应性天然抗体（XNA）和补体的初始损伤。然而，有人认为，先天免疫细胞能够在缺乏XNA和补体的情况下识别和激活异种内皮。在这里，我们表明，猪主动脉内皮细胞（PAECs）直接激活人类中性粒细胞。这种接触依赖性激活引起瞬时钙升高，导致活性氧代谢物（ROM）产生增加。使用腺苷酸尿苷酸丰富的元素为基础的微阵列的中性粒细胞基因表达谱揭示了一个显着的变化，在暴露于PAEC的中性粒细胞基因谱。PAEC依赖的中性粒细胞转录活性通过实时聚合酶链反应进一步证实，其揭示了许多炎性细胞因子的mRNA信息的快速增加。PAEC对人嗜中性粒细胞的激活不依赖于半乳糖α 1，3-半乳糖（Gal α 1，3-gal）结构，因为包含饱和浓度的抗Gal α 1，3-gal 1抗体没有显著影响。此外，在钙螯合剂1，2-双（O-氨基苯基-乙烷-乙烷）-N，N，N ′，N ′-四乙酸-乙酰氧基甲酯和ROM抑制剂二亚丙基碘鎓存在下，这种活化被抑制。我们的数据说明了在不存在XNA和补体的情况下PAEC对先天免疫细胞的直接激活，并表明PAEC和人先天免疫细胞之间的替代识别位点。
The role of inmate immune cells in the recognition and activation of xenogeneic endothelium has always been considered secondary to the initial insult of xenoreactive natural antibodies (XNA) and complement. It was argued, however, that innate immune cells are capable of recognizing and activating xenogeneic endothelium in the absence XNA and complement. Here, we show that porcine aortic endothelial cells (PAECs) activate human neutrophils directly. This contact-dependent activation causes a transient calcium rise leading to increased reactive oxygen metabolite (ROM) production. Neutrophil gene-expression profiling using an adenylate uridylate-rich element-based microarray revealed a dramatic change in the neutrophil gene profiles upon exposure to PAECs. The PAEC-dependent neutrophil transcriptional activity was further confirmed by real-time polymerase chain reaction, which revealed a rapid increase in the mRNA message of a number of inflammatory cytokines. The activation of human neutrophils by PAECs was independent of galactose alpha 1,3-galactose (Gal alpha 1,3-gal) structures, as inclusion of saturating concentrations of anti-Gal alpha 1,3-gal 1 antibodies had no significant effect. Furthermore, this activation was inhibited in the presence of the calcium chelator 1,2-bis(O-aminophenyl-ethane-ethane)-N,N,N',N'-tetraacetic acid-acetoxymethyl ester and the ROM inhibitor diphelylene iodonium. Our data illustrate the direct activation of innate immune cells by PAECs in the absence of XNA and complement and suggest alternative recognition sites between PAECs and human innate immune cells.