Schröder J M
Department of Dermatology, University of Kiel, Germany.
Biochem Pharmacol. 1999 Jan 15;57(2):121-34. doi: 10.1016/s0006-2952(98)00226-3.
Surfaces of higher eukaryotes such as plants, invertebrates, and vertebrates, including humans, are normally covered with microorganisms but usually are not infected by them. The reason, apart from physical barriers, is the production of gene-encoded antimicrobial peptides by epithelial cells. Many novel antimicrobial peptides have been discovered recently in the epithelia of plants, insects, amphibians, and cattle, and, more recently, also in humans. In situ hybridization studies indicate a rather organ-specific expression of the genes for peptide antibiotics, which, due to their antimicrobial spectrum and conditions of expression, may also define the physiologic microflora. Some epithelial antimicrobial peptides are constitutively expressed; others are inducible, either by the presence of microorganisms via as of yet not well characterized elicitor receptors or by endogenous proinflammatory cytokines. Most antimicrobial peptides kill microorganisms by forming pores in the cell membrane, and the sensitivity of some peptide antibiotics towards cholesterol, a major mammalian cell membrane constituent, may indicate why these peptide antibiotics are not toxic for mammalian cells. Thus, it seems to be difficult for microorganisms to acquire resistance, making these peptides very attractive for therapeutic use as antibiotics. The first clinical studies are very promising, and after solving the problems of a large-scale biotechnical synthesis, which is more complicated due to the principally suicidal activity of these peptides, a number of new natural structure-based peptides may be developed. Furthermore, discovery of the inducibility of many antimicrobial peptides may also lead to the development of compounds that elicit epithelial defense reactions by stimulating the synthesis of endogenous peptide antibiotics.
高等真核生物如植物、无脊椎动物和脊椎动物（包括人类）的体表通常覆盖着微生物，但通常不会被它们感染。除了物理屏障外，原因是上皮细胞会产生基因编码的抗菌肽。最近在植物、昆虫、两栖动物和牛的上皮组织中发现了许多新型抗菌肽，最近在人类中也有发现。原位杂交研究表明，肽抗生素基因具有相当器官特异性的表达，由于它们的抗菌谱和表达条件，也可能决定生理微生物群。一些上皮抗菌肽是组成性表达的；其他的是可诱导的，要么是通过尚未明确特征的诱导受体的微生物存在，要么是通过内源性促炎细胞因子。大多数抗菌肽通过在细胞膜上形成孔来杀死微生物，一些肽抗生素对胆固醇（一种主要的哺乳动物细胞膜成分）的敏感性可能表明为什么这些肽抗生素对哺乳动物细胞无毒。因此，微生物似乎很难获得抗性，这使得这些肽作为抗生素在治疗上非常有吸引力。首批临床研究非常有前景，在解决大规模生物技术合成的问题后（由于这些肽的主要自杀活性，这一过程更加复杂），可能会开发出许多基于新天然结构的肽。此外，许多抗菌肽可诱导性的发现也可能导致开发出通过刺激内源性肽抗生素的合成来引发上皮防御反应的化合物。
