Pathogenic natural antibodies recognizing annexin IV are required to develop intestinal ischemia-reperfusion injury.
Pathogenic natural antibodies recognizing annexin IV are required to develop intestinal ischemia-reperfusion injury.
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DOI：
10.4049/jimmunol.0803980
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发表时间：
2009-05-01
期刊：
影响因子：
--
通讯作者：
Holers VM
中科院分区：
文献类型：
--
作者：
Kulik L;Fleming SD;Moratz C;Reuter JW;Novikov A;Chen K;Andrews KA;Markaryan A;Quigg RJ;Silverman GJ;Tsokos GC;Holers VM
当天然IgM抗体识别缺血细胞上显示的新表位时，肠缺血-再灌注（IR）3损伤开始。这些新表位变得易于识别的靶分子和机制尚未得到很好的理解。提出分离的肠上皮细胞（IEC）可能携带IR相关的新表位，我们使用体外IEC结合测定来筛选从未操作的野生型C57 BL/6小鼠的B细胞产生的杂交瘤。我们通过流式细胞术分析鉴定了一种新型IgM单克隆抗体（mAb B4），该抗体可与IEC表面反应，并且单独能够在其他IR抗性Rag 1 −/−小鼠中引起补体激活、中性粒细胞募集和肠损伤。发现单克隆抗体B4特异性识别小鼠膜联蛋白IV。预注射重组膜联蛋白IV阻断了野生型C57 BL/6小鼠的IR损伤，证明了在复杂的天然抗体库的背景下，需要识别这种蛋白质才能产生IR损伤。还发现人类表现出识别膜联蛋白IV的IgM天然抗体。这些数据全部确定膜联蛋白IV作为关键的缺血相关的靶抗原，其在体内发展肠IR损伤所需的病理过程中被天然抗体识别。
Intestinal ischemia-reperfusion (IR)3 injury is initiated when natural IgM antibodies recognize neo-epitopes that are revealed on ischemic cells. The target molecules and mechanisms whereby these neo-epitopes become accessible to recognition are not well understood. Proposing that isolated intestinal epithelial cells (IEC) may carry IR-related neo-epitopes, we used in vitro IEC binding assays to screen hybridomas created from B cells of unmanipulated wild type C57BL/6 mice. We identified a novel IgM monoclonal antibody (mAb B4) that reacted with the surface of IEC by flow cytometric analysis and was alone capable of causing complement activation, neutrophil recruitment and intestinal injury in otherwise IR-resistant Rag1−/− mice. Monoclonal Ab B4 was found to specifically recognize mouse annexin IV. Pre-injection of recombinant annexin IV blocked IR injury in wild type C57BL/6 mice, demonstrating the requirement for recognition of this protein in order to develop IR injury in the context of a complex natural antibody repertoire. Humans were also found to exhibit IgM natural antibodies that recognize annexin IV. These data in toto identify annexin IV as a key ischemia-related target antigen that is recognized by natural Abs in a pathologic process required in vivo to develop intestinal IR injury.
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影响因子：
--
作者：
HERNANDEZ, LA;GRISHAM, MB;GRANGER, DN
通讯作者：
GRANGER, DN
影响因子：
37.8
作者：
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通讯作者：
PINCKARD, RN
影响因子：
4.4
作者：
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通讯作者：
Tsokos, GC
影响因子：
19.6
作者：
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通讯作者：
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影响因子：
4.4
作者：
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通讯作者：
Austen, William G., Jr.