Intestinal Failure and Clinical Nutrition Group, Murdoch Children's Research Institute, Parkville, Australia.
Inflamm Bowel Dis. 2010 Apr;16(4):604-12. doi: 10.1002/ibd.21114.
A33 antigen is a transmembrane protein expressed predominantly in normal intestinal epithelium and most colon cancers and cell lines. The function of A33 antigen is unclear, but indirect evidence indicates a role in cell adhesion, trafficking, and the gut immune response. The aim of this study was to determine the contribution made by A33 antigen in mediating colonic repair following colitis induction in the A33 antigen-deficient mutant mouse.
Colitis was induced by treatment with TNBS/ethanol. A33 antigen-deficient or wildtype mice were sacrificed at 0, 3, 7, and 14 days after colitis induction and morphological damage, mucosal proliferation, and inflammatory cell infiltration were quantified. In a subsequent study, following the induction of colitis mice were monitored for 22 days and morbidity and mortality determined.
Mice lacking A33 antigen expression were compromised in their ability to resolve TNBS-induced damage and exhibited distinct crypt pathology. In A33 antigen-deficient mice morphological damage remained unresolved at 14 days postcolitis induction. Increases in colonic cell proliferation were delayed in A33 antigen-deficient mice, and the rate of crypt fission was increased after TNBS treatment. Commensurate with these observations, polymorphonuclear cell infiltration was suppressed in the absence of A33 antigen. Mortality following colitis induction was 20% higher in A33 antigen-deficient mice than in wildtype controls.
Mice deficient in A33 antigen expression show impaired resolution of hapten-induced mucosal damage, leading to increased mortality, associated with impaired epithelial cell proliferation and a suppressed adaptive immune response. This study suggests a contribution for A33 antigen in the colonic healing response following mucosal damage.
A33 抗原是一种跨膜蛋白，主要在正常肠道上皮细胞和大多数结肠癌和细胞系中表达。A33 抗原的功能尚不清楚，但间接证据表明其在细胞黏附、运输和肠道免疫反应中发挥作用。本研究旨在确定 A33 抗原在缺乏 A33 抗原的突变小鼠结肠炎诱导后的结肠修复中所起的作用。
用 TNBS/乙醇处理诱导结肠炎。在结肠炎诱导后 0、3、7 和 14 天，处死 A33 抗原缺陷型或野生型小鼠，量化形态损伤、黏膜增殖和炎症细胞浸润。在随后的研究中，在诱导结肠炎后监测小鼠 22 天，确定发病率和死亡率。
缺乏 A33 抗原表达的小鼠在解决 TNBS 诱导的损伤方面能力受损，表现出明显的隐窝病理学。在 A33 抗原缺陷型小鼠中，形态损伤在结肠炎诱导后 14 天仍未得到解决。A33 抗原缺陷型小鼠的结肠细胞增殖增加延迟，TNBS 处理后隐窝分裂率增加。与这些观察结果一致，缺乏 A33 抗原时多形核细胞浸润受到抑制。结肠炎诱导后，A33 抗原缺陷型小鼠的死亡率比野生型对照组高 20%。
缺乏 A33 抗原表达的小鼠表现出对半抗原诱导的黏膜损伤的愈合能力受损，导致死亡率增加，这与上皮细胞增殖受损和适应性免疫反应抑制有关。本研究表明 A33 抗原在黏膜损伤后的结肠愈合反应中发挥作用。
