Protective mechanisms in inflammatory lung diseases at airway and alveolar area

我们利用临床标本对炎症性肺疾病(间质性肺炎)的发病机制进行了研究，目的是针对进行性或保护性细胞因子的变化和蛋白水解酶-抗蛋白酶的失衡。采用半定量计分方法对31例(IPF 16例，SSC以外的CVD 9例，SSC 6例)的肺组织病理结果进行评分。肺泡腔巨噬细胞减少和纤维化程度减轻可能是导致BALF淋巴细胞增多的原因之一。纤维化程度不同的UIP/CVD非SSC患者较IPF/UIP和UIP-SSC患者对BALF淋巴细胞增多的贡献更大。我们用RT-PCR方法检测了正常成人肺泡II型细胞系(A549)和原代培养的人肺泡II型细胞中MMP3和TIMP-3mRNA的表达。IL-1β促进基质降解，而转化生长因子-β通过调节基质金属蛋白酶-3和基质金属蛋白酶-3之间的平衡抑制基质降解。我们研究了香烟烟雾提取物(…)的细胞毒性作用。在肺泡II型细胞来源的细胞系(A549)上有更多的CSE)。肺泡上皮细胞凋亡可能是吸烟致肺损伤的机制之一。这种细胞毒性效应可能是由于CSE中存在的或在CSE暴露的细胞中形成的醛和氧化剂之间的相互作用所致。我们比较了从手术活检细胞中获得的肺成纤维细胞的功能。我们比较了UIP患者(n=5)、NSIP患者(n=5)和正常对照组(n=5)手术活检标本中肺成纤维细胞的功能。与NSIP或对照组相比，UIP获得的成纤维细胞表现出更强的收缩能力，F-action含量增加。经免疫印迹法鉴定为纤维连接蛋白(ED-A结构域)和转化生长因子-β1(TGF-β1)。UIP细胞的收缩能力与纤维连接蛋白或转化生长因子-β1的含量呈正相关。因此，UIP成纤维细胞表现出比NSIP成纤维细胞或转化生长因子-β1细胞更强的收缩能力。因此，UIP成纤维细胞表现出比NSIP成纤维细胞和上调的对照成纤维细胞更强的收缩能力。较少

We investigated on the pathogenesis of inflammatory lung diseases (interstitial pneumonias) using clinical samples, aiming at progressive or protective cytokine profiles and protease-antiprotease imbalance. We scored histopathological findings of lung specimens obtaind from 31 cases (16 IPF, 9 CVD other than SSc and 6 SSc) using a semiquaqntitative scoring method. Fewer macrophages in the alveolar spaces and a decrease in the degree of fibrosis may contribute to BALF lymphocytosis more in patients with in the degree of fibrosis may contribute to BALF lymphocytosis more in patients with UIP/CVD non-SSc than in patients with IPF/UIP and UIP-SSc. We examined mRNA expressions of MMP-3 and TIMP-3 in a cell line (A549) and in primary culture of normal adult human type II pneumocytes using RT-PCR. The matrix degradation is enhanced by IL-1beta and suppressed by TGF-betal via regulations in the balance between MMP-3 and TIMP-3. We investigated the cytotoxic effects of cigarette smoke extract ( … More CSE) on an alveolar type II cell-derived cell line (A549). Apoptosis of alveolar epithelial cells may be one of the mechanisms of lung injuury induced by cigarette smoking. This cytotoxic effect might be due to an interaction between aldehydes and oxidants present in CSE or formed in CSE-exposed cells. We compared the function of lung fibroblasts obtained from surgically biopsied cells. We compared the function of lung fibroblasts obtained from surgically biopsied specimens of patients with UIP (n=5), NSIP (n=5), and normal control (n=5). Fibroblasts obtained from UIP showed increased contractility compared with those obtained from NSIP or controls with enhanced F-action content in fibroblasts. The products representing the contractility were identified as fibronectin (ED-A domain) and TGF-betal by immunoblots. The contractility positively korrelated with the amount of either fibronectin or TGF-beta 1. Thus, UIP fibroblasts showed greater contractility than did NSIP fibroblasts or TGF-beta 1. Thus, UIP fibroblasts showed greater contractility than did NSIP fibroblasts and up-regulated control fibroblasts. Less