Lipid mediator-induced expression of bactericidal/permeability-increasing protein (BPI) in human mucosal epithelia
Lipid mediator-induced expression of bactericidal/permeability-increasing protein (BPI) in human mucosal epithelia
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DOI：
10.1073/pnas.052533799
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发表时间：
2002-03-19
影响因子：
11.1
通讯作者：
Colgan, SP
中科院分区：
文献类型：
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作者：
Canny, G;Levy, O;Colgan, SP
衬在粘膜表面的上皮细胞是抵抗细菌入侵和感染的第一道防线。最近的研究还表明，上皮细胞对正在进行的炎症过程的协调有重要作用。在这里，我们证明，人类上皮细胞表达杀菌，渗透性增加蛋白（BPI），抗菌和内毒素中和分子先前与中性粒细胞。此外，我们证明，这种BPI的表达是由内源性抗炎类花生酸（阿司匹林触发脂氧素，ATLa）的类似物转录调节。验证微阵列分析的初步研究显示，广泛来源的上皮细胞（口腔、肺和胃肠道粘膜）表达BPI，并且每一种都受到阿司匹林触发的脂氧素的类似调节。针对BPI定位的研究表明，这种表达发生在培养的上皮细胞系的细胞表面，并且主要定位于人粘膜组织中的上皮。采用BPI中和抗血清的功能研究表明，表面BPI阻断上皮细胞内毒素介导的信号传导并杀死鼠伤寒沙门氏菌。这些研究确定了一个以前不受重视的“分子盾”，保护粘膜表面免受革兰氏阴性菌及其内毒素的侵害。
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 antiserum 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.