Ball S L, Siou G P, Wilson J A, Howard A, Hirst B H, Hall J
Epithelial Research Group, Institute for Cell & Molecular Biosciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
J Laryngol Otol. 2007 Oct;121(10):973-8. doi: 10.1017/S0022215107006184. Epub 2007 Feb 26.
Recurrent acute tonsillitis is one of the most frequent ENT referrals, yet its pathogenesis remains poorly understood, and tonsillectomy still costs the National Health Service more than pound 60,000000 annually. Antimicrobial cationic peptides are components of the innate immune system. They are generally small, highly positively charged peptides with broad spectrum antimicrobial activity which function as the body's 'natural antibiotics'. The role of antimicrobial cationic peptides in the susceptibility of patients to recurrent acute tonsillitis is unknown.
To characterise and compare antimicrobial cationic peptide expression and localisation in human palatine tonsils from control subjects and recurrent acute tonsillitis patients, and to assess the potential role of these peptides in the pathogenesis of tonsillitis.
Palatine tonsils were harvested with informed consent from 19 recurrent acute tonsillitis patients and from five control subjects undergoing tonsillectomy for sleep disorders. Total ribonucleic acid was isolated and antimicrobial cationic peptide expression was characterised using reverse transcription polymerase chain reaction. Fluorescent immunohistochemical techniques were used to localise antimicrobial cationic peptides within fresh frozen tonsil sections.
Using molecular analyses, the palatine tonsils from control and recurrent acute tonsillitis subjects were confirmed as a site of expression of the antimicrobial cationic peptides human beta-defensin 1-3, LL-37 (cathelicidin) and Liver expressed antimicrobial peptide-1 (LEAP-1). We also demonstrated for the first time the expression of Liver expressed antimicrobial peptide-2 (LEAP-2). Our analyses indicated that all six antimicrobial cationic peptides were expressed in all 26 tonsil samples. Immunohistochemical staining indicated that the antimicrobial cationic peptides were localised to the tonsil surface and crypt epithelium. However, the surface epithelium of tonsils from recurrent acute tonsillitis patients showed reduced amounts of antimicrobial peptides human beta-defensins 1 and 3, and LL-37, compared with healthy controls.
The tonsil epithelium synthesizes an array of antimicrobial cationic peptides which function as host defence. Preliminary immunohistochemical data suggest that the surface epithelium of tonsils from recurrent acute tonsillitis patients contains reduced amounts of such peptides, which may increase these patients' susceptibility to infection.
复发性急性扁桃体炎是耳鼻喉科最常见的转诊疾病之一,但其发病机制仍知之甚少,扁桃体切除术每年仍使国民医疗服务体系花费超过6000万英镑。抗菌阳离子肽是先天性免疫系统的组成部分。它们通常是小的、带高度正电荷的肽,具有广谱抗菌活性,起到人体“天然抗生素”的作用。抗菌阳离子肽在复发性急性扁桃体炎患者易感性中的作用尚不清楚。
对健康对照者和复发性急性扁桃体炎患者腭扁桃体中抗菌阳离子肽的表达及定位进行表征和比较,并评估这些肽在扁桃体炎发病机制中的潜在作用。
在获得知情同意后,从19例复发性急性扁桃体炎患者和5例因睡眠障碍接受扁桃体切除术的对照者中采集腭扁桃体。分离总核糖核酸,采用逆转录聚合酶链反应表征抗菌阳离子肽的表达。使用荧光免疫组织化学技术在新鲜冷冻的扁桃体切片中定位抗菌阳离子肽。
通过分子分析,证实健康对照者和复发性急性扁桃体炎患者的腭扁桃体是抗菌阳离子肽人β-防御素1-3、LL-37(杀菌肽)和肝脏表达抗菌肽-1(LEAP-1)的表达部位。我们还首次证明了肝脏表达抗菌肽-2(LEAP-2)的表达。我们的分析表明,所有六种抗菌阳离子肽在所有26个扁桃体样本中均有表达。免疫组织化学染色表明,抗菌阳离子肽定位于扁桃体表面和隐窝上皮。然而,与健康对照相比,复发性急性扁桃体炎患者扁桃体的表面上皮中抗菌肽人β-防御素1和3以及LL-37的含量减少。
扁桃体上皮合成一系列作为宿主防御的抗菌阳离子肽。初步免疫组织化学数据表明,复发性急性扁桃体炎患者扁桃体的表面上皮中此类肽的含量减少,这可能增加这些患者的感染易感性。