Anti-phospholipid antibodies restore mesenteric ischemia/ reperfusion-induced injury in complement receptor 2 complement receptor 1-deficient mice
Anti-phospholipid antibodies restore mesenteric ischemia/ reperfusion-induced injury in complement receptor 2 complement receptor 1-deficient mice
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DOI：
10.4049/jimmunol.173.11.7055
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发表时间：
2004-12-01
影响因子：
4.4
通讯作者：
Tsokos, GC
中科院分区：
文献类型：
--
作者：
Fleming, SD;Egan, RP;Tsokos, GC
补体受体2缺陷（Cr2(-/-)）小鼠对肠系膜缺血/再灌注（I/R）损伤具有抗性，因为它们缺乏天然Ab库的组成部分。目前尚不清楚参与I/R损伤的抗体的性质，也不清楚在Cr2（-/-）小鼠中缺乏识别的靶Ag的组成。由于抗磷脂抗体已被证明可以介导妊娠小鼠的胎儿生长迟缓和丧失，我们进行了实验，以确定抗磷脂抗体是否也可以重建I/R损伤，从而代表Cr2（-/-）小鼠中缺失的损伤诱导库的成员。我们证明了小鼠和人抗带负电荷磷脂的单克隆和多克隆抗体可以重建肠/ r诱导的Cr2（-/-）小鼠肠和肺组织损伤。此外，抗β 2糖蛋白I的抗体可恢复Cr2（-/-）小鼠的局部和远程组织损伤。与Cr2（-/-）小鼠不同，抗损伤小鼠rag1 (-/-) I/R组织损伤的重建需要同时注入抗β -糖蛋白I和抗磷脂抗体。我们得出结论，抗磷脂抗体可以与遭受I/R损伤的组织结合并介导组织损伤。
Complement receptor 2-deficient (Cr2(-/-)) mice are resistant to mesenteric ischemia/reperfusion (I/R) injury because they lack a component of the natural Ab repertoire. Neither the nature of the Abs that are involved in I/R injury nor the composition of the target Ag, to which recognition is lacking in Cr2(-/-) mice, is known. Because anti-phospholipid Abs have been shown to mediate fetal growth retardation and loss when injected into pregnant mice, we performed experiments to determine whether antiphospholipid Abs can also reconstitute I/R injury and, therefore, represent members of the injury-inducing repertoire that is missing in Cr2(-/-) mice. We demonstrate that both murine and human monoclonal and polyclonal Abs against negatively charged phospholipids can reconstitute mesenteric I/R-induced intestinal and lung tissue damage in Cr2(-/-) mice. In addition, Abs against beta2 glycoprotein I restore local and remote tissue damage in the Cr2(-/-) mice. Unlike Cr2(-/-) mice, reconstitution of I/R tissue damage in the injury-resistant Rag-1(-/-) mouse required the infusion of both anti-beta2-glycoprotein I and anti-phospholipid Ab. We conclude that anti-phospholipid Abs can bind to tissues subjected to I/R insult and mediate tissue damage.