Abstract：
Antimicrobial peptides (AMPs) are a promising alternative to antibiotics in the fight against multi-drug resistant and immune system-evading bacterial infections. Protegrins are porcine cathelicidins which have been identified in porcine leukocytes. Protegrin-1 is the best characterized family member and has broad antibacterial activity by interacting and permeabilizing bacterial membranes. Many host defense peptides (HDPs) like LL-37 or chicken cathelicidin 2 (CATH-2) have also been shown to have protective biological functions during infections. In this regard, it is interesting to study if Protegrin-1 has the immune modulating potential to suppress unnecessary immune activation by neutralizing endotoxins or by influencing the macrophage functionality in addition to its direct antimicrobial properties. This study showed that Protegrin-1 neutralized lipopolysaccharide- (LPS) and bacteria-induced activation of RAW macrophages by binding and preventing LPS from cell surface attachment. Furthermore, the peptide treatment not only inhibited bacterial phagocytosis by murine and porcine macrophages but also interfered with cell surface and intracellular bacterial survival. Lastly, Protegrin-1 pre-treatment was shown to inhibit the amastigote survival in Leishmania infected macrophages. These experiments describe an extended potential of Protegrin-1\'s protective role during microbial infections and add to the research towards clinical application of cationic AMPs.
摘要：
抗菌肽（AMPs）在对抗多药耐药和免疫系统逃避细菌感染方面是一种有前途的抗生素替代品。蛋白质是已在猪白细胞中鉴定的猪导管素。Protegrin-1是特征最好的家族成员，通过相互作用和透化细菌膜具有广泛的抗菌活性。许多宿主防御肽（HDP）如LL-37或鸡导管素2（CATH-2）也已显示在感染期间具有保护性生物学功能。在这方面,研究Protegrin-1是否具有免疫调节潜力,通过中和内毒素或通过影响巨噬细胞功能以及其直接的抗菌特性来抑制不必要的免疫激活,这一点很有趣.这项研究表明，Protegrin-1通过结合并阻止LPS细胞表面附着，中和了脂多糖（LPS）和细菌诱导的RAW巨噬细胞活化。此外，肽处理不仅抑制了鼠和猪巨噬细胞的细菌吞噬，而且干扰了细胞表面和细胞内细菌的存活。最后,Protegrin-1预处理显示抑制利什曼原虫感染的巨噬细胞中的假牙存活。这些实验描述了Protegrin-1在微生物感染过程中的保护作用的扩展潜力，并增加了阳离子AMP临床应用的研究。
