Surfactant protein B in type II pneumocytes and intra-alveolar surfactant forms of human lungs

Surfactant protein B in type II pneumocytes and intra-alveolar surfactant forms of human lungs
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DOI:
10.1165/rcmb.2003-0262oc
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发表时间:
2004-04-01
影响因子:
6.4
通讯作者:
Ochs, M
Ochs, M
中科院分区:
医学1区
文献类型:
--
作者:
Brasch, F;Johnen, G;Ochs, M

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表面活性蛋白B(SP - B)由Ⅱ型肺泡上皮细胞合成为前体蛋白(proSP - B),经蛋白水解加工成为一种8 - kD的蛋白质。在人Ⅱ型肺泡上皮细胞中,我们不仅鉴定出了proSP - B、proSP - B的加工中间体以及成熟的SP - B,还鉴定出了N - 末端前肽的片段。通过免疫电子显微镜观察,proSP - B和加工中间体定位于人肺Ⅱ型肺泡上皮细胞的内质网、高尔基体囊泡以及少数多泡体中。在多泡体、复合小体以及一些板层小体中发现了N - 末端前肽片段与成熟SP - B的共定位。成熟的SP - B定位于板层小体的突起核心以及管状髓磷脂结构中的类核心结构上。与对人Ⅱ型肺泡上皮细胞的免疫电子显微镜观察和蛋白质印迹分析结果一致,在分离的大鼠板层小体中也检测到了N - 末端前肽的一个片段。总之,我们的数据表明proSP - B的加工发生在高尔基体和多泡体之间,并提供了证据表明N - 末端前肽的一个片段和成熟的SP - B一起被运输到板层小体。在人肺中,成熟的SP - B通过形成核心颗粒参与板层小体和管状髓磷脂的结构组织。
Surfactant protein B (SP-B) is synthesized by type II pneumocytes as a proprotein (proSP-B) that is proteolytically processed to an 8-kD protein. In human type II pneumocytes, we identified not only proSP-B, processing intermediates of proSP-B, and mature SP-B, but also fragments of the N-terminal propeptide. By means of immunoelectron microscopy, proSP-B and processing intermediates were localized in the endoplasmic reticulum, Golgi vesicles, and few multivesicular bodies in type II pneumocytes in human lungs. A colocalization of fragments of the N-terminal propeptide and mature SP-B was found in multivesicular, composite, and some lamellar bodies. Mature SP-B was localized over the projection core of lamellar bodies and core-like structures in tubular myelin figures. In line with immunoelectron microscopy and Western blot analysis of human type II pneumocytes, a fragment of the N-terminal propeptide was also detected in isolated rat lamellar bodies. In conclusion, our data indicate that the processing of proSP-B occurs between the Golgi complex and multivesicular bodies and provide evidence that a fragment of the N-terminal propeptide and mature SP-B are transported together to the lamellar bodies. In human lungs, mature SP-B is involved in the structural organization of lamellar bodies and tubular myelin by the formation of core particles.