Viscardi Rose, Manimtim Winston, He Ju Ren, Hasday Jeffrey D, Sun Chen-Chih J, Joyce Belinda, Pierce Richard A
Department of Pediatrics, University of Maryland School of Medicine, 22 South Greene Street, Baltimore, 21201, USA.
Pediatr Dev Pathol. 2006 Mar-Apr;9(2):143-51. doi: 10.2350/10-05-0112.1. Epub 2006 Jun 16.
Respiratory colonization of preterm infants with Ureaplasma urealyticum is a significant risk factor for bronchopulmonary dysplasia, a chronic lung disease characterized by arrest of alveolar development, variable interstitial fibrosis, and disordered elastic fibers in the distal airspaces. As indicated in previous studies, moderate to severe fibrosis is a hallmark of pathology in the Ureaplasma-infected preterm lung. To further characterize the preterm lung's response to Ureaplasma, lung specimens from 4 gestational controls (GC), 12 other pneumonia and 5 Ureaplasma-infected infants were analyzed by immunohistochemistry for alpha-smooth muscle actin (alphaSMA) and transforming growth factor beta1 (TGFbeta1), Hart's elastin staining, and in situ hybridization for tropoelastin (TE) expression. Cells positive for alphaSMA were observed in thickened, extensive bundles surrounding terminal airspaces in Ureaplasma and other pneumonia cases compared to individual myofibroblasts in GC. The myofibroblast pattern correlated with the severity of fibrosis, but not duration of ventilation. Transforming growth factor beta1 immunostaining was primarily localized to alveolar macrophages and was increased in Ureaplasma more than in other pneumonia cases. Elastic fibers and TE-expressing cells were spatially limited to emerging septal tips in GC. In pneumonia cases, increased deposition of elastic fibers was observed surrounding terminal airspaces, but TE expression was similar to GC. In Ureaplasma specimens, accumulation of elastic fibers correlated with duration of ventilation, and TE expression was extensive throughout the walls of terminal airspaces. These findings suggest that Ureaplasma is associated with alveolar macrophage TGFbeta1 immunostaining and myofibroblast proliferation contributing to abnormal septation, interstitial fibrosis, and a prolonged and strong elastogenic response in the preterm lung.
解脲脲原体在早产儿呼吸道定植是支气管肺发育不良的一个重要危险因素，支气管肺发育不良是一种慢性肺部疾病，其特征为肺泡发育停滞、不同程度的间质纤维化以及远端气腔内弹性纤维紊乱。如先前研究所示，中重度纤维化是解脲脲原体感染的早产儿肺部病理的一个标志。为了进一步明确早产儿肺部对解脲脲原体的反应，通过免疫组织化学分析了4例孕周对照（GC）、12例其他肺炎患儿和5例解脲脲原体感染患儿的肺标本，检测α-平滑肌肌动蛋白（αSMA）和转化生长因子β1（TGFβ1）、哈特弹性蛋白染色以及原弹性蛋白（TE）表达的原位杂交。与GC组单个肌成纤维细胞相比，在解脲脲原体感染组和其他肺炎组中，在终末气腔周围增厚的广泛束状结构中观察到αSMA阳性细胞。肌成纤维细胞模式与纤维化严重程度相关，但与通气时间无关。转化生长因子β1免疫染色主要定位于肺泡巨噬细胞，且在解脲脲原体感染组中比其他肺炎组中增加。弹性纤维和表达TE 的细胞在GC组中在空间上局限于新出现的间隔尖端。在肺炎病例中，在终末气腔周围观察到弹性纤维沉积增加，但TE表达与GC组相似。在解脲脲原体标本中，弹性纤维的积累与通气时间相关，且TE表达在终末气腔壁上广泛存在。这些发现表明，解脲脲原体与肺泡巨噬细胞转化生长因子β1免疫染色和肌成纤维细胞增殖有关，导致早产肺出现异常分隔、间质纤维化以及延长且强烈的弹性生成反应。
