Yu Yanlei, Chen Yin, Mikael Paiyz, Zhang Fuming, Stalcup Apryll M, German Rebecca, Gould Francois, Ohlemacher Jocelyn, Zhang Hong, Linhardt Robert J
School of Food Science and Biological Engineering, Zhejiang Gongshang University, No. 18 Xuezheng Street, Xiasha High Education Zone, Hangzhou, Zhejiang 310018, China.
Departments of Chemistry, Biology, Chemical Engineering, and Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, NY 12180, USA.
Glycobiology. 2017 Jan;27(1):57-63. doi: 10.1093/glycob/cww104. Epub 2016 Oct 15.
Heparin, a member of a family of molecules called glycosaminoglycans, is biosynthesized in mucosal mast cells. This important anticoagulant polysaccharide is primarily produced by extraction of the mast cell-rich intestinal mucosa of hogs. There is concern about our continued ability to supply sufficient heparin to support the worldwide growth of advanced medical procedures from the static population of adult hogs used as food animals. While the intestinal mucosa of adult pigs is rich in anticoagulant heparin (containing a few hundred milligrams per animal), little is known about how the content of heparin changes with animal age. Using sophisticated mass spectral analysis we discovered that heparin was largely absent from the intestinal mucosa of piglets. Moreover, while the related, nonanticoagulant heparan sulfate glycosaminoglycan was present in significant amounts we found little chondroitin sulfate E also associated with mast cells. Histological evaluation of piglet intestinal mucosa showed a very low mast cell content. Respiratory mast cells have been reported in baby pigs suggesting that there was something unique about the piglets used in the current study. These piglets were raised in the relatively clean environment of a university animal facility and treated with antibiotics over their lifetime resulting in a depleted microbiome that greatly reduced the number of mast cells and heparin content of the intestinal mucosal in these animals. Thus, from the current study it remains unclear whether the lack of intestinal mast cell-derived heparin results from the young age of these animals or their exposure to their depleted microbiome.
肝素是一种名为糖胺聚糖的分子家族成员，在黏膜肥大细胞中生物合成。这种重要的抗凝血多糖主要通过提取富含肥大细胞的猪肠黏膜来生产。人们担心，以食用成年猪为固定来源，我们是否有持续供应足够肝素以支持全球先进医疗程序增长的能力。虽然成年猪的肠黏膜富含抗凝血肝素（每只动物含几百毫克），但肝素含量如何随动物年龄变化却知之甚少。通过精密的质谱分析，我们发现仔猪的肠黏膜中基本没有肝素。此外，虽然相关的非抗凝血硫酸乙酰肝素糖胺聚糖大量存在，但我们发现与肥大细胞相关的硫酸软骨素E很少。对仔猪肠黏膜的组织学评估显示肥大细胞含量极低。有报道称仔猪存在呼吸道肥大细胞，这表明本研究中使用的仔猪有其独特之处。这些仔猪是在大学动物设施相对清洁的环境中饲养的，并且一生都使用抗生素，导致微生物群落减少，极大地降低了这些动物肠黏膜中的肥大细胞数量和肝素含量。因此，从目前的研究来看，尚不清楚肠黏膜中缺乏源自肥大细胞的肝素是由于这些动物年龄小还是由于它们接触了减少的微生物群落。
