HUMAN ALVEOLAR MACROPHAGES SYNTHESIZE FACTOR-VII INVITRO - POSSIBLE ROLE IN INTERSTITIAL LUNG-DISEASE
HUMAN ALVEOLAR MACROPHAGES SYNTHESIZE FACTOR-VII INVITRO - POSSIBLE ROLE IN INTERSTITIAL LUNG-DISEASE
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DOI：
10.1172/jci111922
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发表时间：
1985-01-01
影响因子：
15.9
通讯作者：
FAIR, DS
中科院分区：
文献类型：
--
作者：
CHAPMAN, HA;ALLEN, CL;FAIR, DS
纤维蛋白和组织巨噬细胞在慢性炎症性肺疾病的组织病理学中都是重要的。体外检测新鲜洗涤的人肺泡巨噬细胞的促凝活性。完整的巨噬细胞(5倍。巨噬细胞促凝血活性至少部分不依赖于外源性凝血因子VII，这可通过缺乏凝血因子VII的血浆的平均凝血时间99 S和抗凝血因子VII的抗体中和促凝血活性的中和来判断。用抗凝血因子VII的抗体对代谢性地标记甲硫氨酸的巨噬细胞提取物进行免疫沉淀，并经十二烷基硫酸钠-聚丙烯酰胺凝胶电泳分析，发现了一种标记蛋白，其大小与已知的血因子VII的分子量48,000一致。添加50微克未标记的、纯化的凝血因子VII阻碍了48,000 mW蛋白质的恢复。此外，6名正常志愿者的巨噬细胞培养上清液具有凝血因子X激活活性，在50微米香豆素存在下培养后，X因子激活活性平均被抑制71%，或完全被第VII因子抗体所抑制，表明该细胞合成的第VII因子具有生物活性。内毒素在体外诱导细胞组织因子的增加，但对巨噬细胞因子VII的活性没有一致的影响。9例有临床和/或组织学证据的结节病患者新鲜洗涤的肺泡细胞中组织因子和因子VII的活性。9名受试者中有4名表达组织因子升高，其中7名表达高于正常范围的凝血因子VII活性(P<；0.01)。与结节病患者细胞相关的平均因子VII估计为4.7 ng/106细胞(范围0.4-20)，而正常人的平均值为0.74 ng/106细胞(范围0.2-2)。与先前显示合成纤溶酶原激活剂的数据一起，这些发现表明，人肺泡巨噬细胞正常地合成和表达可测量数量的调节纤维蛋白沉积和纤维蛋白再吸收的蛋白分解反应的初始酶。在一小部分结节病患者中，凝血因子VII活性的异常增加了巨噬细胞调节纤维蛋白周转的可能性，这可能与本病和其他间质性肺疾病的病理有关。
Both fibrin and tissue macrophages are prominent in the histopathology of chronic inflammatory pulmonary disease. The procoagulant activity of freshly lavaged human alveolar macrophages was examined in vitro. Intact macrophages (5 .times. 105 cells) from 13 healthy volunteers promoted clotting of whole plasma in a mean of 65 s. Macrophage procoagulant activity was at least partially independent of exogenous factor VII as judged by a mean clotting time of 99 s in factor VII-deficient plasma and by neutralization of procoagulant activity by an antibody to factor VII. Immunoprecipitation of extracts of macrophages metabolically labeled with [35S]methionine by factor VII antibody and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a labeled protein consistent in size with the known MW of blood factor VII, 48,000. The addition of 50 .mu.g of unlabeled, purified factor VII blocked recovery of the 48,000 MW protein. In addition, supernatants of cultured macrophages from 6 normal volunteers had factor X-activating activity that was suppressed an average of 71% after culture in the presence of 50 .mu.M coumadin or entirely by the factor VII antibody indicating that factor VII synthesized by the cell was biologically active. Endotoxin in vitro induced increases in cellular tissue factor but had no consistent effect on macrophage factor VII activity. The tissue factor and factor VII activities of freshly lavaged alveolar cells from 9 subjects with clinical and/or histologic evidence of sarcoidosis. Four of the 9 subjects expressed increased tissue factor and 7 of 9 had increased factor VII activity over the normal range (P < 0.01). The mean factor VII associated with the cells of sarcoid patients was estimated to be 4.7 ng/106 cells (range 0.4-20) as compared to a mean of 0.74 ng/106 cells (range 0.2-2) for that of normal subjects. Along with previous data showing synthesis of plasminogen activator, these findings indicate that human alveolar macrophages normally synthesize and express measurable amounts of the initial enzymes of proteolytic reactions regulating both fibrin deposition and fibrin resorption. Abnormalities in factor VII activity in a small group of patients with sarcoidosis raise the possiblity that modulation of fibrin turnover by macrophages may contribute to the pathology of this and perhaps other interstitial lung diseases.