cellular prion protein expression as a novel marker of pulmonary fibrosis and clinical significance of cellular prion proein during pulmonary fibrosis

正常和纤维化仓鼠肺中朊病毒蛋白（PrPc）的细胞亚型表达。在未处理的肺中，Clara细胞染色阳性，Clara细胞优先分布在小细支气管中，以球状颗粒为特征。反应产物弥散于颗粒和核外的细胞质中。在博莱霉素诱导的肺纤维化中，在终末细支气管周围增厚的纤维组织中诱导细支气管增生。该事件的特征为导管结构蓄积，其主要内衬代表Clara细胞的PrPc阳性细胞。此外，PrPc阳性细胞偶见于肺泡导管上皮和上皮化的肺泡。这些结果表明，克拉拉细胞可能经历增殖和迁移到腺泡从终末细支气管。纤维组织含有许多α-平滑肌肌动蛋白阳性肌成纤维细胞。本研究表明，PrPc在正常和纤维化仓鼠肺的Clara细胞中均有表达，提示Clara细胞可能作为肺干细胞增殖并修复肺泡损伤后受损的上皮细胞，本研究作为临床医学研究，旨在利用切除标本PrPc表达情况来评价放化疗患者的合理照射面积和剂量。但在肺泡管上皮及上皮化肺泡中未见PrPc阳性细胞，RT-PCR也未检测到PrPc mRNA。这种结果可能是由于放化疗后约8周完全肺纤维化所致。我们打算估计在放化疗后不久，在完全肺纤维化之前，切除的标本。

Cellular isoform of prion protein (PrPc) expression in normal and fibrotic hamster lungs. In untreated lungs, Clara cells, which were preferentially distributed in small bronchioles and characterized by globule granules, were positively stained. Reactive products were diffused in the cytoplasm outside the granules and nuclei. In bleomycin-induced pulmonary fibrosis, bronchiolar proliferation was induced in the thickened fibrous tissue around terminal bronchioles. This event was characterized by accumulation of ductular structures which were predominantly lined by PrPc positive cells representative of Clara cells. Furthermore, PrPc positive cells were occasionally populated in the epithelium of alveolar ducts and reepithelialized alveoli. These findings suggest that Clara cells might undergo proliferation and migration into acini from terminal bronchioles. The fibrous tissue contained many alpha-smooth muscle actin positive myofibroblasts. The present study indicated that PrPc is expressed in Clara cells in normal and fibrotic hamster lungs and suggests that Clara cells may proliferate as pulmonary stem cells and repair the damaged epithelium after alveolar injuries.As clinical medical research this study aimed to evaluate the reasonable radiation area and dose for the patients who were treated with chemoradiation therapy using PrPc expression of resected specimens. But no PrPc positive cells were populated in the epithelium of alveolar ducts and reepithelialized alveoli immunohistochemically; furthermore PrPc mRNA was not detected by RT-PCR. This consequence may be caused by complete pulmonary fibrosis about 8 weeks after chemoradiation therapy. We intend to estimate the esected specimens soon after chemoradiation therapy, just before the complete pulmonary fibrosis.