Matthijsen R A, Derikx J P M, Steffensen R, van Dam R M, Dejong C H C, Buurman W A
Department of Surgery, Maastricht University Medical Centre & School for Nutrition & Metabolism (NUTRIM), Maastricht, The Netherlands.
Mol Immunol. 2009 Jul;46(11-12):2244-8. doi: 10.1016/j.molimm.2009.04.010. Epub 2009 May 23.
Mannose-binding lectin (MBL) deficiency is associated with reduced intestinal ischemia-reperfusion (IR) damage in rodents. We set out to investigate an association between frequently observed MBL deficiency and IR associated intestinal cell damage in man. Using a newly developed IR model of the human small intestine 29 patients were consecutively included. Part of the jejunum was subjected to 30 min of ischemia and reperfusion. The MBL genotype was assessed by means of quantitative-PCR analysis. Enterocyte loss was explored by measuring plasma intestinal-fatty acid binding protein (I-FABP) levels. Arterial and venous MBL plasma levels were measured to assess MBL consumption, MBL deposition was analyzed by immunofluorescence. Ethical approval and informed consent were obtained. The amount of epithelial cell damage varied significantly between the carriers of different mbl2 genotypes (ANOVA, p=0.02). I-FABP release, representing disintegration of differentiated enterocytes, observed in homozygous wildtype individuals was twice (p=0.03) that measured in heterozygous and ten times (p=0.04) that observed in homozygous variant individuals. No MBL deposition was observed over the course of reperfusion. The data indicate that MBL influences intestinal epithelial cell integrity in an immediate and non-complement dependent manner during ischemia and reperfusion.
甘露糖结合凝集素(MBL)缺乏与啮齿动物肠道缺血再灌注(IR)损伤减轻有关。我们着手研究人类中常见的MBL缺乏与IR相关的肠道细胞损伤之间的关联。使用新开发的人类小肠IR模型,连续纳入了29例患者。空肠的一部分经历30分钟的缺血和再灌注。通过定量PCR分析评估MBL基因型。通过测量血浆肠脂肪酸结合蛋白(I-FABP)水平来探究肠上皮细胞损失。测量动脉和静脉MBL血浆水平以评估MBL消耗,通过免疫荧光分析MBL沉积。获得了伦理批准和知情同意。不同mbl2基因型携带者之间上皮细胞损伤量差异显著(方差分析,p = 0.02)。在纯合野生型个体中观察到的代表分化肠上皮细胞解体的I-FABP释放量是杂合子个体的两倍(p = 0.03),是纯合变异个体的十倍(p = 0.04)。在再灌注过程中未观察到MBL沉积。数据表明,在缺血和再灌注期间,MBL以直接且非补体依赖的方式影响肠道上皮细胞完整性。