Mannose-binding lectin binds IgM to activate the lectin complement pathway in vitro and in vivo
Mannose-binding lectin binds IgM to activate the lectin complement pathway in vitro and in vivo
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DOI：
10.1016/j.imbio.2006.06.011
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发表时间：
2006-01-01
期刊：
影响因子：
2.8
通讯作者：
Stahl, Gregory L.
中科院分区：
文献类型：
--
作者：
McMullen, Meghan E.;Hart, Melanie L.;Stahl, Gregory L.
最近的证据表明，MBL依赖性凝集素途径在胃肠道和心肌缺血/再灌注（I/R）诱导的损伤中发挥作用。然而，以前的研究表明IgM和经典途径是I/R后补体激活的起始物。因此，我们研究了MBL和IgM之间导致补体激活的潜在相互作用。使用表面等离子体共振，我们证明MBL结合人IgM。随后，在用小鼠抗人CD 59 IgM致敏人RBC后，在体外证明了功能性补体激活，并且与MBL缺陷（KO）血清相比，用MBL SLI有效血清观察到更多的溶解。类似地，用小鼠抗人CD 59 IgM、MBL和MASP-2处理人内皮细胞活化并沉积C4。这些数据表明，IgM和MBL的存在下，可以激活凝集素途径在体外。胃肠道（G）I/R后，与用MBL-A/C KO血浆复溶的sIgM/MBL-A/C KO小鼠相比，用WT血浆复溶的sIgM/MBL-A/C KO小鼠的血清ALT水平显著升高。类似地，与用MBL-A/C KO血浆处理的sIgM/MBL-A/C KO小鼠相比，用WT血浆重建的sIgM/MBL-A/C KO小鼠的肠C3沉积更大。这些数据首次表明，GI/R诱导的补体激活和随后的损伤都需要IgM和MBL-A/C。(c)2006年Elsevier GmbH。All rights reserved.
Recent evidence has implicated a role for the MBL-dependent lectin pathway in gastrointestinal and myocardial ischemia/reperfusion (I/R)-induced injury. However, previous studies have implicated IgM and the classical pathway as initiators of complement activation following I/R. Thus, we investigated the potential interaction between MBL and IgM leading to complement activation. Using surface plasmon resonance, we demonstrate that MBL does bind human IgM. Subsequently, functional complement activation was demonstrated in vitro following sensitization of human RBCs with mouse anti-human CD59 IgM and more lysis was observed with MBL SLIfficient sera compared to MBL deficient (KO) sera. Similarly, treatment of human endothelial cells with mouse anti-human CD59 IgM, MBL and MASP-2 activated and deposited C4. These data suggest that the presence of both IgM and MBL can activate the lectin pathway in vitro. Serum ALT levels increased significantly in sIgM/MBL-A/C KO mice reconstituted with WT plasma compared to slgM/MBL-A/C KO mice reconstituted with MBL-A/C KO plasma following gastrointestinal (G) I/R. Similarly, intestinal C3 deposition was greater in sIgM/MBL-A/C KO mice reconstituted with WT plasma compared to sIgM/MBL-A/C KO mice treated with MBL-A/C KO plasma. These data indicate for the first time that both IgM and MBL-A/C are required for GI/R-induced complement activation and subsequent injury. (c) 2006 Elsevier GmbH. All rights reserved.