T-cell-mediated mucosal immunity is attenuated in experimental necrotizing enterocolitis
T-cell-mediated mucosal immunity is attenuated in experimental necrotizing enterocolitis
复制标题
DOI：
10.1007/s00383-003-1004-7
复制
发表时间：
2003-07-01
影响因子：
1.8
通讯作者：
Rintala, R
中科院分区：
文献类型：
--
作者：
Anttila, A;Kauppinen, H;Rintala, R
在早产儿坏死性小肠结肠炎（NEC）的胃肠粘膜屏障是不成熟的，但很少有人知道不成熟的肠道免疫反应。本研究的目的是评价实验性NEC肠粘膜免疫反应。在全身麻醉下，通过将牛酪蛋白注射到回肠末端，在6头新生仔猪中诱导NEC。6个对照组接受等量生理盐水。4小时后，从经处理肠袢的肉眼观察最受影响的部分和肉眼观察健康的未经处理肠中取样。采用猪CD 1、CD 2、CD 4、CD 8、CD 45和IgM的单克隆抗体进行免疫组化染色。酪蛋白治疗的肠表现出典型的NEC的宏观和微观结果。在盐水处理的肠中未发现变化。在两组中，治疗区外的肠道正常。在酪蛋白处理的动物中，与盐水处理的对照组相比，酪蛋白处理的样品显示CD4（+）细胞密度显著降低。CD2（+）和CD8（+）细胞的变化趋势相似，但无统计学意义。与对照组相比，酪蛋白处理组中肉眼可见的健康近端未处理样本中的CD 2（+）、CD 4（+）和CD 8（+）淋巴细胞密度显著降低。在酪蛋白处理的动物中，未注射肠中的CD45（+）细胞密度也降低，但未达到统计学显著性。酪蛋白处理组和生理盐水处理组的CD1（+）和IgM（+）细胞密度没有差异。在本NEC模型中发现了显著的T细胞减少。令人惊讶的是，这在酪蛋白注射段之外的宏观健康肠中最为突出。T细胞减少的原因尚不清楚，但已知牛酪蛋白含有可调节免疫功能的肽组分。这些发现可能对新生儿配方奶粉的设计有影响。
In premature infants with necrotizing enterocolitis (NEC) the gastrointestinal mucosal barrier is immature, but little is known about the immune response of immature bowel. The aim of this study was to evaluate the intestinal mucosal immune response in experimental NEC. In general anaesthesia, NEC was induced in six newborn piglets by injection of bovine casein into terminal ileum. Six controls received an equal amount of saline. Four hours later, samples were taken from the macroscopically most affected part of the treated loop and from the macroscopically healthy untreated intestine. Monoclonal antibodies to porcine CD1, CD2, CD4, CD8, CD45 and IgM were used for immunohistochemical staining. Casein-treated bowel showed typical macro- and microscopic findings of NEC. No changes were found in the saline-treated bowel. In both groups the bowel outside the treatment sector was normal. In casein-treated animals, treated samples showed significant decrease in density of CD4(+) cells when compared with saline-treated controls. Similar trend was found in CD2(+) and CD8(+) cells but without statistical significance. Macroscopically healthy proximal untreated samples showed significant decrease in densities of CD2(+), CD4(+) and CD8(+) lymphocytes in casein-treated group when compared with control samples. In casein-treated animals the density of CD45(+) cells in the non-injected bowel was also decreased, but this did not reach statistical significance. Densities of CD1(+) and IgM(+) cells did not differ between casein-treated and saline-treated groups. A significant T-cell decrease was found in the present NEC model. Surprisingly, this was most prominent in the macroscopically healthy bowel outside the casein injection segment. The reason for T-cell decrease remains unclear, but bovine casein is known to contain peptide fractions that can modulate immune function. These findings may have implications in the design of neonatal milk formulas.