Lehrer Robert I, Ganz Tomas
Department of Medicine, Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California, USA.
Curr Opin Hematol. 2002 Jan;9(1):18-22. doi: 10.1097/00062752-200201000-00004.
The cytoplasmic granules of mammalian neutrophils contain several antimicrobial peptides. Some, like defensins, are fully processed before storage, whereas others are stored as precursors that require additional processing. Cathelicidins are bipartite molecules with an N-terminal cathelin domain and an antimicrobial C-terminal domain. Humans apparently have only one cathelicidin gene. Its product, hCAP-18, is present in the secondary (specific) granules of neutrophils, and its C-terminal antimicrobial peptide, LL-37, is liberated by proteinase 3 coincident with degranulation and secretion. Many nonmyeloid tissues also express hCAP-18, including epididymis, spermatids, keratinocytes, epithelial cells, and various lymphocytes. LL-37 stimulates chemotaxis, acting via the formyl peptide-like receptor-1. The structurally diverse cathelicidin-derived antimicrobial peptides of animals provide interesting models for pharmaceutical development. PR-39, a proline-rich porcine cathelicidin, has shown efficacy in limiting myocardial damage after experimental ischemia in rodent models. Porcine protegrins are in stage III clinical trials to prevent oral mucositis caused by radiation or chemo-therapy.
哺乳动物中性粒细胞的胞质颗粒含有多种抗菌肽。一些抗菌肽，如防御素，在储存前已完全加工，而其他抗菌肽则以前体形式储存，需要进一步加工。杀菌肽是由N端的cathelin结构域和C端的抗菌结构域组成的双功能分子。人类显然只有一个杀菌肽基因。其产物hCAP-18存在于中性粒细胞的二级（特异性）颗粒中，其C端抗菌肽LL-37在脱颗粒和分泌时由蛋白酶3释放出来。许多非髓系组织也表达hCAP-18，包括附睾、精子细胞、角质形成细胞、上皮细胞和各种淋巴细胞。LL-37通过甲酰肽样受体-1发挥作用，刺激趋化性。动物体内结构多样的杀菌肽衍生抗菌肽为药物开发提供了有趣的模型。富含脯氨酸的猪杀菌肽PR-39在啮齿动物模型实验性缺血后限制心肌损伤方面已显示出疗效。猪防御素正在进行III期临床试验，以预防放疗或化疗引起的口腔粘膜炎。
