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. 1991 Jan;213(1):81–85. doi: 10.1097/00000658-199101000-00014

Role of granulocyte elastase in tissue injury in patients with septic shock complicated by multiple-organ failure.

H Tanaka 1, H Sugimoto 1, T Yoshioka 1, T Sugimoto 1
PMCID: PMC1358315  PMID: 1985543

Abstract

To better understand the role of granulocyte elastase (GE) in mediating tissue injury during sepsis, GE levels were measured in plasma and bronchoalveolar lavage fluid (BALF) in patients with septic shock (n = 16) and hemorrhagic shock (n = 30). Granulocyte elastase levels were compared to levels of alpha 1-protease inhibitor (alpha 1-PI). Results show that although plasma GE-alpha 1-PI complex was initially elevated in patients with hemorrhagic and septic shock, elevations in plasma GE-alpha 1-PI complex (831 +/- 241 micrograms/L) persisted in septic shock patients. alpha 1-Protease inhibitor levels in serum were increased, resulting in an inhibition of serum GE activity. Granulocyte elastase activity in BALF, however, was significantly higher in those patients with septic, as compared to hemorrhagic shock (31.4 +/- 25.8 versus 3.7 +/- 4.0 U/L, respectively). In addition GE levels were compared to other parameters, including respiratory index, blood neutrophil count, and plasma levels of endotoxin, fibronectin, and coagulation factor XIII. Significant correlations were observed between GE-alpha 1-PI and increased endotoxin concentration and decreased fibronectin and coagulation factor XIII levels. Significant correlation was found also between GE activity in BALF and respiratory index. These findings suggest that severe tissue damage occurred in patients with septic shock complicated by multiple-organ failure. Although GE activity appeared to be adequately inhibited by alpha 1-PI in blood, increased GE activity in local tissues, such as lung alveoli, may be responsible for significant local tissue injury during septic shock.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adeyemi E. O., Hull R. G., Chadwick V. S., Hughes G. R., Hodgson H. J. Circulating human leucocyte elastase in rheumatoid arthritis. Rheumatol Int. 1986;6(2):57–60. doi: 10.1007/BF00541505. [DOI] [PubMed] [Google Scholar]
  2. Bohn H. Isolierung und Charakterisierung des fibrinstabilisierenden Faktors aus menschlichen Thrombozyten. Thromb Diath Haemorrh. 1970 Jun 30;23(3):455–468. [PubMed] [Google Scholar]
  3. Carrell R. W. alpha 1-Antitrypsin: molecular pathology, leukocytes, and tissue damage. J Clin Invest. 1986 Dec;78(6):1427–1431. doi: 10.1172/JCI112731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carrico C. J., Meakins J. L., Marshall J. C., Fry D., Maier R. V. Multiple-organ-failure syndrome. Arch Surg. 1986 Feb;121(2):196–208. doi: 10.1001/archsurg.1986.01400020082010. [DOI] [PubMed] [Google Scholar]
  5. Duswald K. H., Jochum M., Schramm W., Fritz H. Released granulocytic elastase: an indicator of pathobiochemical alterations in septicemia after abdominal surgery. Surgery. 1985 Nov;98(5):892–899. [PubMed] [Google Scholar]
  6. Eiseman B., Sloan R., Hansbrough J., McIntosh R. Multiple organ failure: clinical and experimental. Am Surg. 1980 Jan;46(1):14–19. [PubMed] [Google Scholar]
  7. Fry D. E., Pearlstein L., Fulton R. L., Polk H. C., Jr Multiple system organ failure. The role of uncontrolled infection. Arch Surg. 1980 Feb;115(2):136–140. doi: 10.1001/archsurg.1980.01380020006003. [DOI] [PubMed] [Google Scholar]
  8. Goldfarb M. A., Ciurej T. F., McAslan T. C., Sacco W. J., Weinstein M. A., Cowley R. A. Tracking respiratory therapy in the trauma patient. Am J Surg. 1975 Mar;129(3):255–258. doi: 10.1016/0002-9610(75)90234-2. [DOI] [PubMed] [Google Scholar]
  9. Gramse M., Havemann K., Egbring R. Alpha-2-plasmin-inhibitor inactivation by human granulocyte elastase. Adv Exp Med Biol. 1984;167:253–261. doi: 10.1007/978-1-4615-9355-3_21. [DOI] [PubMed] [Google Scholar]
  10. Ikegami K., Ikemura K., Shimazu T., Shibuya M., Sugimoto H., Yoshioka T., Sugimoto T. Early diagnosis of invasive candidiasis and rapid evaluation of antifungal therapy by combined use of conventional chromogenic limulus test and a newly developed endotoxin specific assay. J Trauma. 1988 Aug;28(8):1118–1126. doi: 10.1097/00005373-198808000-00003. [DOI] [PubMed] [Google Scholar]
  11. Janoff A. Elastase in tissue injury. Annu Rev Med. 1985;36:207–216. doi: 10.1146/annurev.me.36.020185.001231. [DOI] [PubMed] [Google Scholar]
  12. Jochum M., Witte J., Schiessler H., Selbmann H. K., Ruckdeschl G., Fritz H. Clotting and other plasma factors in experimental endotoxemia: inhibition of degradation by exogenous proteinase inhibitors. Eur Surg Res. 1981;13(2):152–168. doi: 10.1159/000128181. [DOI] [PubMed] [Google Scholar]
  13. Kaplan P. D., Kuhn C., Pierce J. A. The induction of emphysema with elastase. I. The evolution of the lesion and the influence of serum. J Lab Clin Med. 1973 Sep;82(3):349–356. [PubMed] [Google Scholar]
  14. Keiser H., Greenwald R. A., Feinstein G., Janoff A. Degradation of cartilage proteoglycan by human leukocyte granule neutral proteases--a model of joint injury. II. Degradation of isolated bovine nasal cartilage proteoglycan. J Clin Invest. 1976 Mar;57(3):625–632. doi: 10.1172/JCI108318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lee C. T., Fein A. M., Lippmann M., Holtzman H., Kimbel P., Weinbaum G. Elastolytic activity in pulmonary lavage fluid from patients with adult respiratory-distress syndrome. N Engl J Med. 1981 Jan 22;304(4):192–196. doi: 10.1056/NEJM198101223040402. [DOI] [PubMed] [Google Scholar]
  16. Mainardi C. L., Hasty D. L., Seyer J. M., Kang A. H. Specific cleavage of human type III collagen by human polymorphonuclear leukocyte elastase. J Biol Chem. 1980 Dec 25;255(24):12006–12010. [PubMed] [Google Scholar]
  17. Mosher D. F. Action of fibrin-stabilizing factor on cold-insoluble globulin and alpha2-macroglobulin in clotting plasma. J Biol Chem. 1976 Mar 25;251(6):1639–1645. [PubMed] [Google Scholar]
  18. Mosher D. F., Schad P. E. Cross-linking of fibronectin to collagen by blood coagulation Factor XIIIa. J Clin Invest. 1979 Sep;64(3):781–787. doi: 10.1172/JCI109524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ohlsson K., Olsson I. The neutral proteases of human granulocytes. Isolation and partial characterization of granulocyte elastases. Eur J Biochem. 1974 Mar 1;42(2):519–527. doi: 10.1111/j.1432-1033.1974.tb03367.x. [DOI] [PubMed] [Google Scholar]
  20. Smedly L. A., Tonnesen M. G., Sandhaus R. A., Haslett C., Guthrie L. A., Johnston R. B., Jr, Henson P. M., Worthen G. S. Neutrophil-mediated injury to endothelial cells. Enhancement by endotoxin and essential role of neutrophil elastase. J Clin Invest. 1986 Apr;77(4):1233–1243. doi: 10.1172/JCI112426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Smith S. F., Guz A., Cooke N. T., Burton G. H., Tetley T. D. Extracellular elastolytic activity in human lung lavage: a comparative study between smokers and non-smokers. Clin Sci (Lond) 1985 Jul;69(1):17–27. doi: 10.1042/cs0690017. [DOI] [PubMed] [Google Scholar]
  22. Sugimoto T., Ogawa M., Shimazaki S., Fujii C., Tahara I. Klinische Untersuchung über die Schockorgane in Beziehung zur Schockdauer. Anaesthesist. 1976 Feb;25(2):51–55. [PubMed] [Google Scholar]
  23. Tanaka H., Shimazu T., Sugimoto H., Yoshioka T., Sugimoto T. A sensitive and specific assay for granulocyte elastase in inflammatory tissue fluid using L-pyroglutamyl-L-prolyl-L-valine-p-nitroanilide. Clin Chim Acta. 1990 Feb 28;187(2):173–180. doi: 10.1016/0009-8981(90)90344-r. [DOI] [PubMed] [Google Scholar]
  24. Weissmann G., Zurier R. B., Hoffstein S. Leukocytic proteases and the immunologic release of lysosomal enzymes. Am J Pathol. 1972 Sep;68(3):539–564. [PMC free article] [PubMed] [Google Scholar]

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