Abstract
Alveolar macrophages are cell's important in immune defense and inflammation in the lung, and the coagulation system participates in these reactions. In earlier experiments, it was found that alveolar macrophages contain and produce tissue factor, the extrinsic clotting pathway activator. The present experiments explore possible production by alveolar macrophages of the sequence of the clotting proteins that interact to form thrombin following initiation of coagulation by tissue factor. In studies using alveolar macrophages purified from rabbits, factor V activity was not detected in cell preparations assayed directly after isolation. However, after short-term culture, we found generation and release of factor V activity by these cells, which was predominantly from subpopulations with densities of 1.060-1.068 g/ml, corresponding to intermediate stages of alveolar macrophage maturation. Cell viability and protein synthesis were required for generation of the activity as shown by inhibitory effects of cell lysis before culture and by effects observed after including puromycin in cultures with viable cells. The activity generated was characterized as factor V by demonstrating specific functional requirements in one- and two-stage coagulation tests. There was no detectable generation in these cultures of factors II, VII, X, or the more recently described factor X- independent monocyte/macrophage prothrombinases. Factor V activity generated by alveolar macrophages may contribute to prothrominase assembly, activation of clotting, and fibrin formation within the alveolus.
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Selected References
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- Bach R., Oberdick J., Nemerson Y. Immunoaffinity purification of bovine factor VII. Blood. 1984 Feb;63(2):393–398. [PubMed] [Google Scholar]
- Bachofen M., Weibel E. R. Structural alterations of lung parenchyma in the adult respiratory distress syndrome. Clin Chest Med. 1982 Jan;3(1):35–56. [PubMed] [Google Scholar]
- Broze G. J., Jr Binding of human factor VII and VIIa to monocytes. J Clin Invest. 1982 Sep;70(3):526–535. doi: 10.1172/JCI110644. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kandall C., Akinbami T. K., Colman R. W. Determinants of prothrombinase activity and modification of prothrombin conversion by thrombin-treated factor V. Br J Haematol. 1972 Dec;23(6):655–668. doi: 10.1111/j.1365-2141.1972.tb03481.x. [DOI] [PubMed] [Google Scholar]
- Maier R. V., Ulevitch R. J. The induction of a unique procoagulant activity in rabbit hepatic macrophages by bacterial lipopolysaccharides. J Immunol. 1981 Oct;127(4):1596–1600. [PubMed] [Google Scholar]
- Meyer E. C., Ottaviano R. The effect of fibrin on the morphometric distribution of pulmonary exudative edema. Lab Invest. 1973 Sep;29(3):320–328. [PubMed] [Google Scholar]
- Nesheim M. E., Katzmann J. A., Tracy P. B., Mann K. G. Factor V. Methods Enzymol. 1981;80(Pt 100):249–274. doi: 10.1016/s0076-6879(81)80023-7. [DOI] [PubMed] [Google Scholar]
- Olson J. P., Miller L. L., Troup S. B. Synthesis of clotting factors by the isolated perfused rat liver. J Clin Invest. 1966 May;45(5):690–701. doi: 10.1172/JCI105384. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Osterud B., Bögwald J., Lindahl U., Seljelid R. Production of blood coagulation factor V and tissue thromboplastin by macrophages in vitro. FEBS Lett. 1981 May 5;127(1):154–160. doi: 10.1016/0014-5793(81)80363-8. [DOI] [PubMed] [Google Scholar]
- Rothberger H., McGee M. P., Lee T. K. Tissue factor activity. A marker of alveolar macrophage maturation in rabbits. Effects of granulomatous pneumonitis. J Clin Invest. 1984 Jun;73(6):1524–1531. doi: 10.1172/JCI111358. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz B. S., Levy G. A., Curtiss L. K., Fair D. S., Edgington T. S. Plasma lipoprotein induction and suppression of the generation of cellular procoagulant activity in vitro: two procoagulant activities are produced by peripheral blood mononuclear cells. J Clin Invest. 1981 Jun;67(6):1650–1658. doi: 10.1172/JCI110201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz B. S., Levy G. A., Fair D. S., Edgington T. S. Murine lymphoid procoagulant activity induced by bacterial lipopolysaccharide and immune complexes is a monocyte prothrombinase. J Exp Med. 1982 May 1;155(5):1464–1479. doi: 10.1084/jem.155.5.1464. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shands J. W., Jr The endotoxin-induced procoagulant of mouse exudate macrophages: a factor-X activator. Blood. 1983 Aug;62(2):333–340. [PubMed] [Google Scholar]
- Sundsmo J. S., Fair D. S. Relationships among the complement, kinin, coagulation and fibrinolytic systems in the inflammatory reaction. Clin Physiol Biochem. 1983;1(2-5):225–284. [PubMed] [Google Scholar]
- Tracy P. B., Rohrbach M. S., Mann K. G. Functional prothrombinase complex assembly on isolated monocytes and lymphocytes. J Biol Chem. 1983 Jun 25;258(12):7264–7267. [PubMed] [Google Scholar]
- Tsao B. P., Fair D. S., Curtiss L. K., Edgington T. S. Monocytes can be induced by lipopolysaccharide-triggered T lymphocytes to express functional factor VII/VIIa protease activity. J Exp Med. 1984 Apr 1;159(4):1042–1057. doi: 10.1084/jem.159.4.1042. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilson D. B., Salem H. H., Mruk J. S., Maruyama I., Majerus P. W. Biosynthesis of coagulation Factor V by a human hepatocellular carcinoma cell line. J Clin Invest. 1984 Mar;73(3):654–658. doi: 10.1172/JCI111256. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zimmerman T. S., Fierer J., Rothberger H. Blood coagulation and the inflammatory response. Semin Hematol. 1977 Oct;14(4):391–408. [PubMed] [Google Scholar]