The Host Defence Peptide LL-37 is Susceptible to Proteolytic Degradation by Wound Fluid Isolated from Foot Ulcers of Diabetic Patients
The Host Defence Peptide LL-37 is Susceptible to Proteolytic Degradation by Wound Fluid Isolated from Foot Ulcers of Diabetic Patients
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DOI：
10.1007/s10989-014-9410-3
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发表时间：
2014-12-01
影响因子：
2.5
通讯作者：
Lundy, Fionnuala T.
中科院分区：
文献类型：
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作者：
McCrudden, Maeliosa T. C.;McLean, Denise T. F.;Lundy, Fionnuala T.
宿主防御肽（HDPs）的多效性，包括杀死微生物、促进再上皮化和增加血管生成的能力，表明这些重要肽在治疗慢性、不愈合伤口方面具有潜在的治疗作用。然而，通过抵抗存在于伤口部位的一系列蛋白酶的降解来维持肽的完整性是临床成功的先决条件。在这项研究中，我们探讨了外源性LL-37（一种HDP）在糖尿病足溃疡创面液中的降解，以确定其对蛋白水解降解的易感性。我们的结果表明，LL-37在糖尿病足溃疡微环境中是不稳定的。伤口液处理一夜后，LL-37完全降解。对裂解位点的分析表明可能涉及宿主和细菌衍生的蛋白酶。降解产物对铜绿假单胞菌有一定的抑菌活性，但对金黄色葡萄球菌无活性。总之，我们的数据表明，在临床研究之前，稳定LL-37序列内选定的肽键将代表未来研究的一个途径，以解决其作为糖尿病伤口外源性应用治疗的潜力。
The pleiotropic effects of host defence peptides (HDPs), including the ability to kill microorganisms, enhance re-epithelialisation and increase angiogenesis, indicates a role for these important peptides as potential therapeutic agents in the treatment of chronic, non-healing wounds. However, the maintenance of peptide integrity, through resistance to degradation by the array of proteinases present at the wound site, is a prerequisite for clinical success. In this study we explored the degradation of exogenous LL-37, one such HDP, by wound fluid from diabetic foot ulcers to determine its susceptibility to proteolytic degradation. Our results suggest that LL-37 is unstable in the diabetic foot ulcer microenvironment. Following overnight treatment with wound fluid, LL-37 was completely degraded. Analysis of cleavage sites suggested potential involvement of both host- and bacterial-derived proteinases. The degradation products were shown to retain some antibacterial activity against Pseudomonas aeruginosa but were inactive against Staphylococcus aureus. In conclusion, our data suggest that stabilising selected peptide bonds within the sequence of LL-37 would represent an avenue for future research prior to clinical studies to address its potential as an exogenously-applied therapeutic in diabetic wounds.