de Crémoux H, Bignon J
Clinique de Pathologie Respiratoire et Environnement, et Unité INSERM 139, Centre Hospitalier Intercommunal, Créteil, France.
Pathol Biol (Paris). 1988 Nov;36(9):1119-23.
Chronic elastolytic activity in the lung is currently believed to be a major factor in pathogenesis of emphysema. Collagenase may have similar role in disorganizing lung collagen network, leading to fibrotic lung diseases (FLD). The possible involvement of collagenase in FLD is suggested by: 1) an increase collagenolitic activity in bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis or adult respiratory distress syndrome; 2) the accumulation and the activation of cells able to produce collagenases in FLD: fibroblasts, macrophages, neutrophils and eosinophils. However the exact role of collagenase in FLD is still unknown: it could inhibit neocollagen deposition, limiting fibrotic process or lead to further destruction of collagen network. Recent data suggest that genomic macrophage activation (such the proto oncogene c-SIS) may lead to several cellular events: 1) increase number and activation of fibroblasts with collagen synthesis; 2) increase collagenase production resulting of accumulation and activation of fibroblasts, macrophages, neutrophils. So we conclude that such a genomic macrophage activation may be the major factor contributing to the collagen network damage leading to lung tissue fibrosis.
目前认为，肺部的慢性弹性蛋白酶活性是肺气肿发病机制中的一个主要因素。胶原酶在破坏肺胶原网络方面可能具有类似作用，从而导致肺纤维化疾病（FLD）。胶原酶可能参与FLD的依据如下：1）特发性肺纤维化或成人呼吸窘迫综合征患者支气管肺泡灌洗液中胶原分解活性增加；2）在FLD中能够产生胶原酶的细胞（成纤维细胞、巨噬细胞、中性粒细胞和嗜酸性粒细胞）的聚集和激活。然而，胶原酶在FLD中的确切作用仍然未知：它可能抑制新胶原沉积，限制纤维化进程，或者导致胶原网络的进一步破坏。最近的数据表明，基因组巨噬细胞激活（如原癌基因c - SIS）可能导致多种细胞事件：1）增加成纤维细胞的数量并激活其胶原合成；2）由于成纤维细胞、巨噬细胞、中性粒细胞的聚集和激活而增加胶原酶的产生。因此，我们得出结论，这种基因组巨噬细胞激活可能是导致胶原网络损伤进而引起肺组织纤维化的主要因素。
