Kobayashi N, Suko M, Sugiyama H, Dohi M, Okudaira H, Miyamoto T
Department of Medicine and Physical Therapy, University of Tokyo School of Medicine, Japan.
Nihon Kyobu Shikkan Gakkai Zasshi. 1990 Jun;28(6):867-74.
Interstitial and intraalveolar fibrin deposition is a prominent feature in adult respiratory distress syndrome and is also observed in the inflammatory phase of interstitial lung disease (ILD). It is suggested that the coagulation abnormality in these disorders may be implicated in the pathogenesis of subsequent fibrosis of the lung. In this study, we examined the procoagulant activity (PCA) of alveolar macrophages during the development of bleomycin-induced lung fibrosis in rats. The PCA of alveolar macrophages was significantly increased at 2, 7 and 14 days after the intratracheal administration of bleomycin compared with that of control rats. The greatest PCA was observed at 7 days after the bleomycin injection, the inflammatory phase in the development of lung fibrosis. Increased PCA returned to the normal value at 21 days, while the fibrotic process advanced and the collagen content increased in the lung. Alveolar macrophages at 7 days after the administration of bleomycin or saline were separated into five density fractions on discontinuous Percoll gradients. The increase in the percentage of low-density macrophages was observed in bleomycin-injected rats. The greatest PCA was demonstrated in the lowest-density fraction (specific gravity less than 1.030), while reduced activities were observed in the higher-density fractions, in each group. The increased PCA of alveolar macrophages during lung injury was due in part to the increase of low-density subpopulation, which had greater PCA, although the fibrin deposition in the development of lung fibrosis remained to be defined, the increase of coagulation pathways may contribute to the progression of interstitial fibrotic lung diseases.
间质和肺泡内纤维蛋白沉积是成人呼吸窘迫综合征的一个显著特征,在间质性肺疾病(ILD)的炎症阶段也可观察到。提示这些疾病中的凝血异常可能与随后的肺纤维化发病机制有关。在本研究中,我们检测了博来霉素诱导的大鼠肺纤维化发展过程中肺泡巨噬细胞的促凝活性(PCA)。与对照大鼠相比,气管内给予博来霉素后2天、7天和14天,肺泡巨噬细胞的PCA显著增加。博来霉素注射后7天观察到最大的PCA,此时处于肺纤维化发展的炎症阶段。PCA增加在21天时恢复到正常水平,而肺内纤维化过程进展且胶原含量增加。给予博来霉素或生理盐水后7天的肺泡巨噬细胞在不连续的Percoll梯度上被分离成五个密度组分。在注射博来霉素的大鼠中观察到低密度巨噬细胞百分比增加。在每组中,最低密度组分(比重小于1.030)显示出最大的PCA,而在较高密度组分中活性降低。肺损伤期间肺泡巨噬细胞PCA增加部分归因于具有更高PCA的低密度亚群增加,尽管肺纤维化发展过程中的纤维蛋白沉积仍有待确定,但凝血途径的增加可能有助于间质性纤维化肺病的进展。