Skip to main content
SpringerLink
Log in

Neutrophil activation in the haemolytic uraemic syndrome: free and complexed elastase in plasma

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

There is evidence of neutrophil involvement in the pathogenesis of the haemolytic uraemic syndrome (HUS), and neutrophil release products are thought to cause endothelial cell damage. Elastase is the major lysosmal proteinase liberated by activated neutrophils. In this study we measured both free and complexed elastase. No free elastase activity could be detected in the plasma of patients with diarrhoea-associated (D+) HUS using a specific substrate. However, there was a marked increase in α1-antitrypsin (α1-AT) complexed elastase as measured by a newly developed enzyme-linked immunosorbent assay not only in D+ HUS, but also in non-diarrhoea-associated (D-) HUS. This finding is independent of either a high polymorphonuclear leucocyte count or renal failure. This increase in bound elastase together with our sequential data which demonstrate raised α1-AT complexed elastase levels early in the disease process further support the theory that neutrophil activation is one of the key events in the pathophysiology of this disorder.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Fong JSC, De Chadarevian JP, Kaplan BS (1982) Hemolytic uremic syndrome: current concepts and management. Pediatr Clin North Am 29:835–856

    PubMed  Google Scholar 

  2. Kaplan BS, Thompson PD, De Chadarevian JP (1976) The hemolytic uremic syndrome. Pediatr Clin North Am:761–777

  3. Levin M, Barratt TM (1984) Haemolytic uraemic syndrome. Arch Dis Child 59:397–400

    PubMed  Google Scholar 

  4. Gianantonio CA, Vitacco M, Mendiharzu F, Rutty A, Mendilharzu J (1964) The hemolytic uremic syndrome. J Pediatr 4:478–491

    Google Scholar 

  5. Piel CF, Phibbs RH (1966) The hemolytic uremic syndrome. Pediatr Clin North Am 13:295–314

    Google Scholar 

  6. Koster F, Levin J, Walker L (1978) Hemolytic uremic syndrome after shigellosis: relation to endotoxaemia and circulating immune complexes. N Engl J Med 298:927–933

    PubMed  Google Scholar 

  7. Walters MDS, Matthei IU, Kay R, Dillon MJ, Barratt TM (1989) Polymorphonuclear leucocyte count in haemolytic uraemic syndrome. Pediatr Nephrol 3:130–134

    PubMed  Google Scholar 

  8. Robson WL, Fick GH, Wilson PC (1988–1989) Prognostic factors in typical post-diarrhea hemolytic-uremic syndrome. Child Nephrol Urol 9:203–207

    Google Scholar 

  9. Harlan JM, Killen PD, Harler LA, Striker GE (1981) Neutrophil mediated endothelial injury in vitro. J Clin Invest 68:1394–1403

    PubMed  Google Scholar 

  10. Vedanaraynanan W, Kaplan BS, Fong BSC (1987) Neutrophil function in an experimental model of hemolytic uremic syndrome. Pediatr Res 21:252–256

    PubMed  Google Scholar 

  11. Forsyth KD, Simpson AC, Fitzpatrick MM, Barratt TM, Levinsky RJ (1989) Neutrophil mediated endothelial injury in haemolytic uraemic syndrome. Lancet II:411–414

    Article  Google Scholar 

  12. Kaplan BS, Mills M (1988) Elevated serum elastase and α1-antitrypsin levels in haemolytic uraemic syndrome. Clin Nephrol 30: 193–196

    PubMed  Google Scholar 

  13. Henson PM, Johnston RB (1987) Tissue injury in inflammation: oxidants, proteinases and cationic proteins. J Clin Invest 79: 669–674

    PubMed  Google Scholar 

  14. Carrel RW (1986) Alpha-1-antitrypsin: molecular pathology, leucocyte and tissue damage. J Clin Invest 78:1427–1431

    PubMed  Google Scholar 

  15. Worthen GS, Haslett C, Rees AJ, Gumbay RS, Henson JE, Henson PM (1987) Neutrophil mediated pulmonary vascular injury. Am Rev Respir Dis 136:19–28

    PubMed  Google Scholar 

  16. Davies M, Barrett AJ, Travis J, Sanders E, Coles GA (1978) The degradation of human glomerular basement membrane with purified lysosomal proteinases: evidence for the pathogenic role of the polymorphonuclear leucocyte in glomerulonephritis. Clin Sci Mol Med 54:233–240

    PubMed  Google Scholar 

  17. Ohlsson K, Olsson I (1977) The extracellular release of granulocyte collagenase and elastase during phagocytosis and inflammatory processes. Scand J Haematol 19:145–152

    PubMed  Google Scholar 

  18. Ohlsson K, Olsson I (1974) Neutral proteases of human granulocyte. III. Interaction between human granulocyte elastase and plasma protease inhibitors. Scand J Clin Lab Invest 34:349–355

    PubMed  Google Scholar 

  19. Brower MS, Harpel PC (1983) Alpha-1-antitrypsin-human leucocyte elastase complexes in blood: quantification by an enzyme linked differential antibody immunosorbent assay and comparison with alpha-2-plasmin inhibitor-plasmin complexes. Blood 61:842–849

    PubMed  Google Scholar 

  20. Johnson RJ, Couser WG, Alpers CE, Vissers M, Schulze M, Klebanoff SJ (1988) The human neutrophil serine proteinases, elastase and cathepsin g, can mediate glomerular injury in vivo. J Exp Med 168:1169–1174

    Article  PubMed  Google Scholar 

  21. Barrett AJ (1981) Leucocyte elastase. In: Lorand L (ed) Methods in enzymology, vol 80. Academic Press, New York, pp 581–584

    Google Scholar 

  22. Karmali MA, Steele BT, Petric M, Lim C (1983) Sporadic cases of haemolytic uraemic syndrome associated with faecal cytotoxin and cytotoxin producingEscherichia coli in stools. Lancet I:619–620

    Google Scholar 

  23. Grandsen WR, Damm MAS, Anderson JD (1986) Further evidence associating hemolytic uremic syndrome with infection by verotoxin producingEscherichia coli 0157: H7. J Infect Dis 155:522–524

    Google Scholar 

  24. Carter AO, Borczyk AA, Carlson JAK (1987) An outbreak ofEscherichia coli 0157:H7-associated haemorrhagic colitis in a nursing home. N Engl J Med 317:1496–1500

    PubMed  Google Scholar 

  25. Smedley LA, Tonnesen MG, Sandhaus RA, Haslet C, Guthrie LA, Johnson PM, Henson PM, Worthen GS (1986) Neutrophil-mediated injury to endothelial cells. J Clin Invest 77:1233–1243

    PubMed  Google Scholar 

  26. Butler T, Islam MR, Azad MAK, Jones PK (1987) Risk factors for the development of hemolytic uremic syndrome during shigellosis. J Pediatr 110:894–897

    PubMed  Google Scholar 

  27. Carrell RW, Jeppsson JO, Laurell CB, Brennan SO, Owen MC, Vaughan L, Ross Boswell D (1982) Structure and variation of human α1-antitrypsin. Nature 298:329–334

    PubMed  Google Scholar 

  28. Milford D, Taylor CM, Rafaat F, Halloran E, Daws J (1989) Neutrophil elastases and haemolytic uraemic syndrome (letter). Lancet II: 1153

    Article  Google Scholar 

  29. Bergstein JM, Kuerderli U, Bang NU (1982) Plasma inhibitor of glomerular fibrinolysis in the haemolytic uraemic syndrome. Am J Med 73:322–327

    PubMed  Google Scholar 

  30. Coad NAG, Marshall T, Rowe B, Taylor CM (1991) Changes in the postenteropathic form of the hemolytic uremic syndrome in children. Clin Nephrol 35:10–16

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Paediatric Nephrology, Institute of Child Health, 30 Guilford Street, WC1N 1EH, London, UK

    Margaret M. Fitzpatrick, Vanita Shah, Guido Filler, Michael J. Dillon & T. Martin Barratt

Authors
  1. Margaret M. Fitzpatrick
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vanita Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Guido Filler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael J. Dillon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T. Martin Barratt
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fitzpatrick, M.M., Shah, V., Filler, G. et al. Neutrophil activation in the haemolytic uraemic syndrome: free and complexed elastase in plasma. Pediatr Nephrol 6, 50–53 (1992). https://doi.org/10.1007/BF00856833

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00856833

Key words

Search

Navigation