Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Curr Pharm Des. 2018;24(10):1100-1120. doi: 10.2174/1381612824666180403123233.
In recent years, the therapeutic potential of antimicrobial peptides (AMPs) as immunomodulators has become generally accepted. Nevertheless, only very few AMP-based compounds have progressed into clinical trials. This paradox may be explained by the fact, that some of the intrinsic properties of natural peptides, such as proteolytic and oxidative instability, render them inconvenient as therapeutics. Therefore, substantial research efforts have been dedicated to mimic the physico-chemical properties as well as biological activities of AMPs by designing and identifying more stable peptidomimetics displaying analogous immunomodulatory activity profiles. Neutrophils play key roles in host defense as major effector cells in clearance of pathogens by phagocytosis and by regulating other processes of innate immunity as well as by promoting resolution of inflammation. Several aspects of these effects are correlated to their expression of formyl peptide receptors (FPRs) that have been shown to be targets of both natural and synthetic antimicrobial peptides. In the present review recent findings highlighting the role of FPRs in mediating immunomodulatory activities of natural and synthetic AMPs as well as of stabilized peptidomimetics are discussed, and prospects for future development of immunomodulatory therapeutics are presented.
近年来，抗菌肽（AMPs）作为免疫调节剂的治疗潜力已被普遍接受。然而，只有极少数基于 AMP 的化合物进入临床试验。这种矛盾可能是由于天然肽的一些固有特性，如蛋白酶和氧化不稳定性，使它们不适合作为治疗剂。因此，人们致力于通过设计和鉴定更稳定的具有类似免疫调节活性的肽模拟物来模拟 AMP 的物理化学性质和生物活性。中性粒细胞作为吞噬作用清除病原体的主要效应细胞，在宿主防御中发挥关键作用，并通过调节其他先天免疫过程以及促进炎症消退来发挥作用。这些作用的几个方面与它们表达的形式肽受体（FPRs）相关，已经证明 FPRs 是天然和合成抗菌肽的靶点。本文综述了 FPR 在介导天然和合成 AMP 以及稳定肽模拟物的免疫调节活性中的作用的最新发现，并提出了免疫调节治疗的未来发展前景。
