Canny Geraldine, Levy Ofer, Furuta Glenn T, Narravula-Alipati Sailaja, Sisson Richard B, Serhan Charles N, Colgan Sean P
Department of Veterinary Physiology, University College of Dublin, Dublin 4, Ireland.
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3902-7. doi: 10.1073/pnas.052533799. Epub 2002 Mar 12.
Epithelial cells which line mucosal surfaces are the first line of defense against bacterial invasion and infection. Recent studies have also indicated that epithelial cells contribute significantly to the orchestration of ongoing inflammatory processes. Here, we demonstrate that human epithelial cells express bactericidal/permeability-increasing protein (BPI), an antibacterial and endotoxin-neutralizing molecule previously associated with neutrophils. Moreover, we demonstrate that such BPI expression is transcriptionally regulated by analogs of endogenously occurring anti-inflammatory eicosanoids (aspirin-triggered lipoxins, ATLa). Initial studies to verify microarray analysis revealed that epithelial cells of wide origin (oral, pulmonary, and gastrointestinal mucosa) express BPI and each is similarly regulated by aspirin-triggered lipoxins. Studies aimed at localization of BPI revealed that such expression occurs on the cell surface of cultured epithelial cell lines and dominantly localizes to epithelia in human mucosal tissue. Functional studies employing a BPI-neutralizing anti-serum revealed that surface BPI blocks endotoxin-mediated signaling in epithelia and kills Salmonella typhimurium. These studies identify a previously unappreciated "molecular shield" for protection of mucosal surfaces against Gram-negative bacteria and their endotoxin.
排列在粘膜表面的上皮细胞是抵御细菌入侵和感染的第一道防线。最近的研究还表明，上皮细胞在正在进行的炎症过程的协调中发挥着重要作用。在此，我们证明人类上皮细胞表达杀菌/通透性增加蛋白（BPI），这是一种先前与中性粒细胞相关的抗菌和内毒素中和分子。此外，我们证明这种BPI表达受内源性抗炎类花生酸（阿司匹林触发的脂氧素，ATLa）类似物的转录调控。验证微阵列分析的初步研究表明，广泛来源（口腔、肺部和胃肠道粘膜）的上皮细胞表达BPI，并且每种细胞都受到阿司匹林触发的脂氧素的类似调控。旨在定位BPI的研究表明，这种表达发生在培养的上皮细胞系的细胞表面，并且主要定位于人类粘膜组织中的上皮细胞。使用BPI中和抗血清的功能研究表明，表面BPI可阻断上皮细胞中内毒素介导的信号传导并杀死鼠伤寒沙门氏菌。这些研究确定了一种以前未被认识的“分子屏障”，用于保护粘膜表面免受革兰氏阴性菌及其内毒素的侵害。
