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. 1994;3(1):11–16. doi: 10.1155/S0962935194000025

Mechanism for the Increased Permeability in Endothelial Monolayers Induced by Elastase

N Suzuki 1,, Y Ishii 1, S Kitamura 1
PMCID: PMC2367014  PMID: 18472917

Abstract

The aim of this study was to investigate the mechanism for the increase in endothelial permeability induced by human neutrophil elastase (HNE). Pretreatment of bovine pulmonary artery endothelial cells (BPAEC) with HNE(0-30 μg/ml) for 1 h produced a concentration dependent increase in 125I-albumin clearance. The effect was reversible and was not due to cytolysis. Pretreatment of BPAEC with sodium tungstate, which depletes xanthine oxidase, or with oxypurinol, did not prevent HNE induced increased permeability. Heparin, which neutralizes the cationic charge of HNE, also had no protective effect. Pretreatment with heat inactivated HNE, which still had positive charge sites, did not result in increased endothelial permeability. Also, ONO-5046, a novel specific inhibitor of HNE, did prevent increased permeability. These results suggest that elastase increases endothelial permeability mainly through its proteolytic effects.

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Selected References

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  1. Baugh R. J., Travis J. Human leukocyte granule elastase: rapid isolation and characterization. Biochemistry. 1976 Feb 24;15(4):836–841. doi: 10.1021/bi00649a017. [DOI] [PubMed] [Google Scholar]
  2. Eiermann G. J., Dickey B. F., Thrall R. S. Polymorphonuclear leukocyte participation in acute oleic-acid-induced lung injury. Am Rev Respir Dis. 1983 Nov;128(5):845–850. doi: 10.1164/arrd.1983.128.5.845. [DOI] [PubMed] [Google Scholar]
  3. Flick M. R., Perel A., Staub N. C. Leukocytes are required for increased lung microvascular permeability after microembolization in sheep. Circ Res. 1981 Mar;48(3):344–351. doi: 10.1161/01.res.48.3.344. [DOI] [PubMed] [Google Scholar]
  4. Fowler A. A., Hyers T. M., Fisher B. J., Bechard D. E., Centor R. M., Webster R. O. The adult respiratory distress syndrome. Cell populations and soluble mediators in the air spaces of patients at high risk. Am Rev Respir Dis. 1987 Nov;136(5):1225–1231. doi: 10.1164/ajrccm/136.5.1225. [DOI] [PubMed] [Google Scholar]
  5. Garcia J. G., Siflinger-Birnboim A., Bizios R., Del Vecchio P. J., Fenton J. W., 2nd, Malik A. B. Thrombin-induced increase in albumin permeability across the endothelium. J Cell Physiol. 1986 Jul;128(1):96–104. doi: 10.1002/jcp.1041280115. [DOI] [PubMed] [Google Scholar]
  6. Havemann K., Gramse M. Physiology and pathophysiology of neutral proteinases of human granulocytes. Adv Exp Med Biol. 1984;167:1–20. doi: 10.1007/978-1-4615-9355-3_1. [DOI] [PubMed] [Google Scholar]
  7. Heflin A. C., Jr, Brigham K. L. Prevention by granulocyte depletion of increased vascular permeability of sheep lung following endotoxemia. J Clin Invest. 1981 Nov;68(5):1253–1260. doi: 10.1172/JCI110371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ishii Y., Partridge C. A., Del Vecchio P. J., Malik A. B. Tumor necrosis factor-alpha-mediated decrease in glutathione increases the sensitivity of pulmonary vascular endothelial cells to H2O2. J Clin Invest. 1992 Mar;89(3):794–802. doi: 10.1172/JCI115658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Johnson J. L., Rajagopalan K. V., Cohen H. J. Molecular basis of the biological function of molybdenum. Effect of tungsten on xanthine oxidase and sulfite oxidase in the rat. J Biol Chem. 1974 Feb 10;249(3):859–866. [PubMed] [Google Scholar]
  10. Kawabata K., Suzuki M., Sugitani M., Imaki K., Toda M., Miyamoto T. ONO-5046, a novel inhibitor of human neutrophil elastase. Biochem Biophys Res Commun. 1991 Jun 14;177(2):814–820. doi: 10.1016/0006-291x(91)91862-7. [DOI] [PubMed] [Google Scholar]
  11. Key N. S., Platt J. L., Vercellotti G. M. Vascular endothelial cell proteoglycans are susceptible to cleavage by neutrophils. Arterioscler Thromb. 1992 Jul;12(7):836–842. doi: 10.1161/01.atv.12.7.836. [DOI] [PubMed] [Google Scholar]
  12. Martodam R. R., Baugh R. J., Twumasi D. Y., Liener I. E. A rapid procedure for the large scale purification of elastase and cathepsin G from human sputum. Prep Biochem. 1979;9(1):15–31. doi: 10.1080/00327487908061669. [DOI] [PubMed] [Google Scholar]
  13. McDonald J. A., Kelley D. G. Degradation of fibronectin by human leukocyte elastase. Release of biologically active fragments. J Biol Chem. 1980 Sep 25;255(18):8848–8858. [PubMed] [Google Scholar]
  14. Meyrick B. Pathology of the adult respiratory distress syndrome. Crit Care Clin. 1986 Jul;2(3):405–428. [PubMed] [Google Scholar]
  15. Ohlsson K. Interactions between granulocyte proteases and protease inhibitors in the lung. Bull Eur Physiopathol Respir. 1980;16 (Suppl):209–222. doi: 10.1016/b978-0-08-027379-2.50022-3. [DOI] [PubMed] [Google Scholar]
  16. Olsson I., Venge P. Cationic proteins of human granulocytes. II. Separation of the cationic proteins of the granules of leukemic myeloid cells. Blood. 1974 Aug;44(2):235–246. [PubMed] [Google Scholar]
  17. Plow E. F. Leukocyte elastase release during blood coagulation. A potential mechanism for activation of the alternative fibrinolytic pathway. J Clin Invest. 1982 Mar;69(3):564–572. doi: 10.1172/JCI110482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rinaldo J. E., Dauber J. H., Christman J., Rogers R. M. Neutrophil alveolitis following endotoxemia. Enhancement by previous exposure to hyperoxia. Am Rev Respir Dis. 1984 Dec;130(6):1065–1071. doi: 10.1164/arrd.1984.130.6.1065. [DOI] [PubMed] [Google Scholar]
  19. Rodell T. C., Cheronis J. C., Ohnemus C. L., Piermattei D. J., Repine J. E. Xanthine oxidase mediates elastase-induced injury to isolated lungs and endothelium. J Appl Physiol (1985) 1987 Nov;63(5):2159–2163. doi: 10.1152/jappl.1987.63.5.2159. [DOI] [PubMed] [Google Scholar]
  20. Skutelsky E., Rudich Z., Danon D. Surface charge properties of the luminal front of blood vessel walls: an electron microscopical analysis. Thromb Res. 1975 Oct;7(4):623–634. doi: 10.1016/0049-3848(75)90108-5. [DOI] [PubMed] [Google Scholar]
  21. Taylor R. G., McCall C. E., Thrall R. S., Woodruff R. D., O'Flaherty J. T. Histopathologic features of phorbol myristate acetate-induced lung injury. Lab Invest. 1985 Jan;52(1):61–70. [PubMed] [Google Scholar]
  22. Twumasi D. Y., Liener I. E. Proteases from purulent sputum. Purification and properties of the elastase and chymotrypsin-like enzymes. J Biol Chem. 1977 Mar 25;252(6):1917–1926. [PubMed] [Google Scholar]
  23. Vedder N. B., Winn R. K., Rice C. L., Chi E. Y., Arfors K. E., Harlan J. M. A monoclonal antibody to the adherence-promoting leukocyte glycoprotein, CD18, reduces organ injury and improves survival from hemorrhagic shock and resuscitation in rabbits. J Clin Invest. 1988 Mar;81(3):939–944. doi: 10.1172/JCI113407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Weiland J. E., Davis W. B., Holter J. F., Mohammed J. R., Dorinsky P. M., Gadek J. E. Lung neutrophils in the adult respiratory distress syndrome. Clinical and pathophysiologic significance. Am Rev Respir Dis. 1986 Feb;133(2):218–225. doi: 10.1164/arrd.1986.133.2.218. [DOI] [PubMed] [Google Scholar]
  25. Weiss S. J., Curnutte J. T., Regiani S. Neutrophil-mediated solubilization of the subendothelial matrix: oxidative and nonoxidative mechanisms of proteolysis used by normal and chronic granulomatous disease phagocytes. J Immunol. 1986 Jan;136(2):636–641. [PubMed] [Google Scholar]
  26. Weiss S. J. Tissue destruction by neutrophils. N Engl J Med. 1989 Feb 9;320(6):365–376. doi: 10.1056/NEJM198902093200606. [DOI] [PubMed] [Google Scholar]
  27. Weitz J. I., Huang A. J., Landman S. L., Nicholson S. C., Silverstein S. C. Elastase-mediated fibrinogenolysis by chemoattractant-stimulated neutrophils occurs in the presence of physiologic concentrations of antiproteinases. J Exp Med. 1987 Dec 1;166(6):1836–1850. doi: 10.1084/jem.166.6.1836. [DOI] [PMC free article] [PubMed] [Google Scholar]

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