Shao J S, Engle M, Xie Q, Schmidt R E, Narisawa S, Millan J L, Alpers D H
Department of Medicine, Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Microsc Res Tech. 2000 Oct 15;51(2):121-8. doi: 10.1002/1097-0029(20001015)51:2<121::AID-JEMT3>3.0.CO;2-8.
The gastrointestinal tract of mammals secretes a phospholipid-rich membrane that is enriched in alkaline phosphatase (AP) and surfactant proteins (surfactant-like particle, SLP). The production of this particle is stimulated in the small intestine by fat feeding and in cultured cells in vitro by transfection with intestinal alkaline phosphatase (IAP). To test whether tissue non-specific alkaline phosphatase (TNAP) was a factor in stimulating surfactant-like particle production in stomach and colon (tissues expressing TNAP), mice lacking this enzyme were studied. Mice were harvested at 8 days of life, when body weight of homozygous animals (TNAP -/-) was about half that of congenic controls (TNAP +/+) or heterozygotes (TNAP +/-), but before seizures had begun. No difference in content of the major SLP protein (65 kDa) by Western blotting or immunocytochemistry was seen in stomach or colon of TNAP -/- vs. TNAP +/+ animals, but the content was only about half in the IAP-expressing small bowel. Transmission electron microscopy of the TNAP -/- small bowel showed large dilated lysosomes and residual bodies. Colonocytes and gastric surface epithelial cells from the same animals showed mitochondria containing homogeneous dense inclusions, consistent with neutral lipid. In the underweight homozygous animals, there was a decrease in the neuronal content of submucosal ganglia in the jejunum and ileum and of myenteric ganglia in the jejunum of TNAP -/- animals. These findings suggest that (1) TNAP is not important in maintaining surfactant-like particle content of tissues that express TNAP, (2) normal fat absorption is important in maintaining SLP content in the small intestine, and (3) TNAP is important in the maintenance of some intestinal structures, and perhaps their function.
哺乳动物的胃肠道会分泌一种富含磷脂的膜，这种膜富含碱性磷酸酶（AP）和表面活性蛋白（表面活性样颗粒，SLP）。在小肠中，脂肪喂养会刺激这种颗粒的产生；在体外培养的细胞中，转染肠碱性磷酸酶（IAP）也会刺激其产生。为了测试组织非特异性碱性磷酸酶（TNAP）是否是刺激胃和结肠（表达TNAP的组织）中表面活性样颗粒产生的一个因素，对缺乏这种酶的小鼠进行了研究。在小鼠出生8天时将其处死，此时纯合动物（TNAP -/-）的体重约为同基因对照（TNAP +/+）或杂合子（TNAP +/-）的一半，但尚未开始出现癫痫发作。通过蛋白质印迹法或免疫细胞化学检测，在TNAP -/-与TNAP +/+动物的胃或结肠中，主要SLP蛋白（65 kDa）的含量没有差异，但在表达IAP的小肠中，该蛋白含量仅约为一半。对TNAP -/-小肠进行透射电子显微镜检查发现有大量扩张的溶酶体和残余小体。来自同一动物的结肠细胞和胃表面上皮细胞显示线粒体含有均匀的致密内含物，与中性脂质一致。在体重不足的纯合动物中，TNAP -/-动物空肠和回肠黏膜下神经节以及空肠肌间神经节中的神经元含量减少。这些发现表明：（1）TNAP对维持表达TNAP的组织中的表面活性样颗粒含量并不重要；（2）正常的脂肪吸收对维持小肠中的SLP含量很重要；（3）TNAP对维持某些肠道结构及其功能可能很重要。
