Cunliffe R N, Mahida Y R
Institute of Infection, Immunity and Inflammation and Division of Gastroenterology, University of Nottingham, United Kingdom.
J Leukoc Biol. 2004 Jan;75(1):49-58. doi: 10.1189/jlb.0503249. Epub 2003 Oct 2.
The gastrointestinal (GI) tract is exposed to a wide range of microorganisms. The expression of antimicrobial peptides has been demonstrated in different regions of the GI tract, predominantly in epithelial cells, which represent the first host cells with which the microorganisms have to interact for invasion. The intestinal epithelial monolayer is complex, consisting of different cell types, and most have a limited lifespan. Of the GI antimicrobial peptides, alpha- and beta-defensins have been studied the most and are expressed by distinct types of epithelial cells. Enteric alpha-defensin expression is normally restricted to Paneth and intermediate cells in the small intestine. However, there are important differences between mice and humans in the processing of the precursor forms of enteric alpha-defensins. Parasite infection induces an increase in the number of enteric alpha-defensin-expressing Paneth and intermediate cells in the murine small intestine. In the chronically inflamed colonic mucosa, metaplastic Paneth cells (which are absent in the normal colon) also express enteric alpha-defensins. Epithelial expression of beta-defensins may be constitutive or inducible by infectious and inflammatory stimuli. The production of some members of the beta-defensin family appears to be restricted to distinct parts of the GI tract. Recent studies using genetically manipulated rodents have demonstrated the likely in vivo importance of enteric antimicrobial peptides in innate host defense against microorganisms. The ability of these peptides to act as chemoattractants for cells of the innate- and adaptive-immune system may also play an important role in perpetuating chronic inflammation in the GI tract.
胃肠道（GI）会接触到种类繁多的微生物。抗菌肽已在胃肠道的不同区域被证实有表达，主要在上皮细胞中，上皮细胞是微生物入侵时首先必须与之相互作用的宿主细胞。肠道上皮单层结构复杂，由不同类型的细胞组成，且大多数细胞寿命有限。在胃肠道抗菌肽中，α-防御素和β-防御素研究得最多，且由不同类型的上皮细胞表达。肠道α-防御素的表达通常局限于小肠的潘氏细胞和中间细胞。然而，在肠道α-防御素前体形式的加工过程中，小鼠和人类存在重要差异。寄生虫感染会导致小鼠小肠中表达肠道α-防御素的潘氏细胞和中间细胞数量增加。在慢性炎症的结肠黏膜中，化生的潘氏细胞（正常结肠中不存在）也表达肠道α-防御素。β-防御素的上皮表达可能是组成性的，也可能由感染和炎症刺激诱导。β-防御素家族的一些成员的产生似乎局限于胃肠道的不同部位。最近使用基因操作啮齿动物的研究表明，肠道抗菌肽在宿主对微生物的固有防御中可能具有重要的体内作用。这些肽作为先天和适应性免疫系统细胞的趋化剂的能力，也可能在胃肠道慢性炎症的持续中起重要作用。
