Human natural IgM can induce ischemia/reperfusion injury in a murine intestinal model.
Human natural IgM can induce ischemia/reperfusion injury in a murine intestinal model.
复制标题
人类天然 IgM 可在小鼠肠道模型中诱导缺血/再灌注损伤。
DOI：
10.1016/j.molimm.2008.06.013
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发表时间：
2008
影响因子：
3.6
通讯作者：
Carroll,MichaelC
中科院分区：
文献类型：
--
作者：
Zhang,Ming;Alicot,ElisabethM;Carroll,MichaelC
缺血/再灌注（I/R）损伤的一种新机制是通过先天性自身免疫来实现的。不同动物I/R模型的研究表明，缺血组织的再灌注引起涉及补体系统的急性炎症反应，补体系统由自身反应性天然IgM激活。类似的机制是否在人类中运作仍是未知的。我们研究了这个重要的问题，通过测试，如果人天然IgM可以诱导I/R损伤，在一个既定的小鼠肠道模型。RAG-1−/−小鼠（免疫球蛋白缺陷），保护其免受I/R损伤，用纯化的正常人IgM重建并置于肠损伤模型中。接受假处理的重建RAG-1−/−小鼠在肠中未显示组织损伤。相比之下，经历40分钟肠缺血和3小时再灌注的重组RAG-1−/−小鼠在局部组织中显示出显著的损伤。免疫组化结果显示I/R组小鼠小肠绒毛中有补体C4沉积，而假手术组则无。因此，我们的研究是第一个报告，描述了人天然IgM能够诱导I/R损伤的肠道模型，并进一步表明先天性自身免疫可能在致病条件下在人类。
A new mechanism of ischemia/reperfusion (I/R) injury is discovered recently operating through innate autoimmunity. Studies of different animal I/R models showed that reperfusion of ischemic tissues elicits an acute inflammatory response involving complement system which is activated by autoreactive natural IgM. Whether similar mechanism operating in human is still unknown. We investigated this important question by testing if human natural IgM could induce I/R injury in an established murine intestinal model. RAG-1−/−mice (immunoglobulin deficient), which are protected from I/R injury, were reconstituted with purified normal human IgM and subjected in an intestinal injury model. Reconstituted RAG-1−/−mice that were underwent sham treatment did not show tissue injury in intestine. In contrast, reconstituted RAG-1−/−mice that underwent 40min intestinal ischemia and 3h reperfusion showed significant injury in the local tissues. In addition, immunohistochemistry showed that complement C4 were deposited in intestinal villi of I/R but not sham treated mice. Therefore, our study is the first report describing that human natural IgM is capable to induce I/R injury in the intestinal model, and further suggests that innate autoimmunity may operate under pathogenic conditions in human.