Academic Unit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, UK.
Histochem Cell Biol. 2012 Nov;138(5):749-58. doi: 10.1007/s00418-012-0990-8. Epub 2012 Jul 6.
Although the biology the PLUNC (recently renamed BPI fold, BPIF) family of secreted proteins is poorly understood, multiple array based studies have suggested that some are differentially expressed in lung diseases. We have examined the expression of BPIFB1 (LPLUNC1), the prototypic two-domain containing family member, in lungs from CF patients and in mouse models of CF lung disease. BPIFB1 was localized in CF lung samples along with BPIFA1, MUC5AC, CD68 and NE and directly compared to histologically normal lung tissues and that of bacterial pneumonia. We generated novel antibodies to mouse BPIF proteins to conduct similar studies on ENaC transgenic (ENaC-Tg) mice, a model for CF-like lung disease. Small airways in CF demonstrated marked epithelial staining of BPIFB1 in goblet cells but staining was absent from alveolar regions. BPIFA1 and BPIFB1 were not co-localised in the diseased lungs. In ENaC-Tg mice there was strong staining of both proteins in the airways and luminal contents. This was most marked for BPIFB1 and was noted within 2 weeks of birth. The two proteins were present in distinct cells within epithelium. BPIFB1 was readily detected in BAL from ENaC-Tg mice but was absent from wild-type mice. Alterations in the expression of BPIF proteins is associated with CF lung disease in humans and mice. It is unclear if this elevation of protein production, which results from phenotypic alteration of the cells within the diseased epithelium, plays a role in the pathogenesis of the disease.
尽管 PLUNC（最近更名为 BPI 折叠，BPIF）家族分泌蛋白的生物学特性知之甚少，但多项基于阵列的研究表明，其中一些在肺部疾病中存在差异表达。我们已经检查了 CF 患者肺组织和 CF 肺部疾病小鼠模型中 BPIFB1（LPLUNC1）的表达，BPIFB1 是含有两个结构域的典型家族成员。BPIFB1 与 CF 肺样本中的 BPIFA1、MUC5AC、CD68 和 NE 一起定位于，与组织学正常的肺组织和细菌性肺炎直接比较。我们生成了针对小鼠 BPIF 蛋白的新型抗体，用于对 ENaC 转基因（ENaC-Tg）小鼠进行类似研究，ENaC-Tg 小鼠是 CF 样肺部疾病的模型。CF 中的小气道显示 BPIFB1 在杯状细胞中的上皮染色明显，但在肺泡区域无染色。BPIFA1 和 BPIFB1 在病变肺组织中没有共定位。在 ENaC-Tg 小鼠中，两种蛋白在气道和管腔内容物中均有强烈染色。BPIFB1 染色最为明显，在出生后 2 周内即可观察到。这两种蛋白存在于上皮细胞的不同细胞中。BPIFB1 可在 ENaC-Tg 小鼠的 BAL 中轻易检测到，但在野生型小鼠中不存在。BPIF 蛋白表达的改变与人类和小鼠的 CF 肺部疾病有关。尚不清楚这种蛋白产生的升高是否源于病变上皮细胞的表型改变，是否在疾病的发病机制中发挥作用。
