Three pentraxins C-reactive protein, serum amyloid p component and pentraxin 3 mediate complement activation using Collectin CL-P1
Three pentraxins C-reactive protein, serum amyloid p component and pentraxin 3 mediate complement activation using Collectin CL-P1
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使用 Collectin CL-P1 三种五聚蛋白 C 反应蛋白、血清淀粉样蛋白 p 成分和五聚蛋白 3 介导补体激活
DOI：
10.1016/j.bbagen.2016.11.023
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
N.
中科院分区：
文献类型：
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作者：
2.Roy;N.;Ohtani;K.;Hidaka;Y.;Amano;Y.;Matsuda;Y.;Mori;K.;Hwang;I.;Inoue;N.;Wakamiya;N.
五聚蛋白（Pentraxins，PTX）是一个多功能的保守蛋白超家族，参与急性时相反应。最近，我们已经表明，collectin胎盘1（CL-P1）和C-反应蛋白（CRP）介导的补体激活，并未能形成终端补体复合物（TCC）在正常血清条件下，因为补体因子H inhibitory.MethodsWe使用CL-P1表达CHO/ldlA 7细胞研究与PTX的相互作用。可溶型CL-P1用于结合、C3和TCC沉积实验的ELISA测定。此外，我们使用我们以前建立的CL-P1表达HEK 293细胞的C3片段和TCC deposition assay.ResultsWe证明，CL-P1也结合血清淀粉样蛋白P组分（SAP）和五聚蛋白3（PTX 3）激活的经典途径和替代途径使用因子B。CRP和PTX 3进一步放大补体沉积备解素。我们发现CRP和PTX 3募集CFH，而SAP募集表达CL-P1的细胞表面上的C4结合蛋白，以防止在正常血清条件下TCC的形成。此外，在ELISA和细胞实验中，CFH、C4 BP和补体因子I（CFI）的消耗未能防止TCC形成。此外，可溶性补体受体1，所有补体途径的抑制剂，防止PTX诱导的TCC formation.ConclusionOur目前的研究假设，pentraxins与CL-P1的相互作用是参与补体activation. GeneralSignificanceCL-P1可能普遍抑制PTX诱导的补体激活和宿主损伤，以保护自身组织。
BackgroundPentraxins (PTXs) are a superfamily of multifunctional conserved proteins involved in acute-phase responses. Recently, we have shown that collectin placenta 1 (CL-P1) and C-reactive protein (CRP) mediated complement activation and failed to form terminal complement complex (TCC) in normal serum conditions because of complement factor H inhibition.MethodsWe used CL-P1 expressing CHO/ldlA7 cells to study the interaction with PTXs. Soluble type CL-P1 was used in an ELISA assay for the binding, C3 and TCC deposition experiments. Furthermore, we used our previously established CL-P1 expressing HEK293 cells for the C3 fragment and TCC deposition assay.ResultsWe demonstrated that CL-P1 also bound serum amyloid p component (SAP) and pentraxin 3 (PTX3) to activate the classical pathway and the alternative pathway using factor B. CRP and PTX3 further amplified complement deposition by properdin. We found that CRP and PTX3 recruit CFH, whereas SAP recruits C4 binding protein on CL-P1 expressing cell surfaces to prevent the formation of TCC in normal serum conditions. In addition, depletion of CFH, C4BP and complement factor I (CFI) failed to prevent TCC formation both in ELISA and cell experiments. Furthermore, soluble complement receptor 1, an inhibitor of all complement pathways prevents PTX induced TCC formation.ConclusionOur current study hypothesizes that the interaction of pentraxins with CL-P1 is involved in complement activation.General significanceCL-P1 might generally inhibit PTX induced complement activation and host damage to protect self-tissues.