Lyberg T, Nakstad B, Hetland O, Boye N P
Department of Surgery, Ullevål University Hospital, Oslo, Norway.
Eur Respir J. 1990 Jan;3(1):61-7.
Fibrin deposition in the alveolar space and the lung interstitium is a prominent feature of many types of inflammatory pulmonary diseases. Cells of the monocyte/macrophage line are the primary cells supplying procoagulant activity in inflammatory lesions. In the present study we found that both lung alveolar macrophages (LAM) and bronchoalveolar lavage fluids (BALF) from humans contained procoagulant activities. The procoagulant in BALF was associated with membrane vesicles which sedimented at 100,000 g for 1 h. By electron microscopy the BALF ultrasediment was seen to consist almost exclusively of membrane material and this was confirmed by monitoring the content of different marker enzymes for specific subcellular structures. Using macrophage membrane markers, at least part of the BALF-ultrasediment was shown to be derived from LAM. On the basis of phospholipase C sensitivity, antibody neutralization and the site of action of the procoagulant in the sequential activation of coagulation factors, both the LAM-associated and the BALF-associated procoagulant activity was identified as thromboplastin (tissue factor) or thromboplastin-factor VII complexes. This suggests that alveolar macrophages and the LAM-derived thromboplastin-containing microvesicles may contribute to intraalveolar and interstitial fibrin deposition in vivo and probably also have consequences for the development of pulmonary fibrosis.
肺泡腔和肺间质中的纤维蛋白沉积是多种炎症性肺部疾病的一个显著特征。单核细胞/巨噬细胞系的细胞是炎症病变中提供促凝活性的主要细胞。在本研究中，我们发现人类的肺泡巨噬细胞（LAM）和支气管肺泡灌洗液（BALF）都含有促凝活性。BALF中的促凝剂与在100,000 g下离心1小时沉淀的膜泡相关。通过电子显微镜观察，BALF超沉淀物几乎完全由膜物质组成，通过监测特定亚细胞结构的不同标记酶的含量证实了这一点。使用巨噬细胞膜标记物，显示至少部分BALF超沉淀物来源于LAM。基于磷脂酶C敏感性、抗体中和以及促凝剂在凝血因子顺序激活中的作用位点，LAM相关和BALF相关的促凝活性均被鉴定为组织因子或组织因子 - VII复合物。这表明肺泡巨噬细胞和LAM衍生的含组织因子的微泡可能在体内促成肺泡内和间质纤维蛋白沉积，并且可能对肺纤维化的发展也有影响。
