Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Granulocyte lysosomal factors and plasma elastase in uremia: A potential factor of catabolism

  • 21 Accesses

  • 13 Citations


In uremic intoxication proteolytic activity in plasma and striated muscle is enhanced. To get further insights into the underlying mechanisms the lysosomal factors of polymorphonuclear (PMN) leukocytes and the plasma elastase-α 1-proteinase inhibitor complex were investigated in patients with acute and chronic renal failure. Lysosomal activity was evaluated in peripheral blood smears by the lysis of erythrocytes and plasma (halo formation) around each neutrophil induced by 0.25 M NaCl borate buffer.

In about half of the patients with chronic renal insufficiency on dietary treatment lysosomal activity of PMN leukocytes was reduced. The plasma concentration of elastase-α 1-proteinase inhibitor complex was normal in most subjects, but increased in three patients with the highest serum creatinine levels (>13 mg/dl).

In the patients with acute renal failure (ARF) of various origin (postoperatively, septicemia, pancreatitis, or dye-induced) halo formation was either reduced or absent. The plasma elastase-α 1-proteinase inhibitor complex was increased in 5/6 of the patients by a factor of two to four. Also in the patients on regular hemodialysis treatment halo formation of PMN leukocytes was substantially reduced, whereas the plasma levels of elastase-α 1-proteinase inhibitor complex was slightly increased.

The finding of reduced lysosomal activity of PMN neutrophils in uremia may be partly due to an enhanced release of neutral proteinases into the circulation as indicated by the elevated plasma levels of elastase-α 1-proteinase inhibitor complex in some patients. This release might be in part due to the effect of “uremic toxins”. In the patients on hemodialysis treatment the contact of the blood with the dialyzer (cuprophane) membrane might be an additional factor. Moreover, in the patients with acute renal failure the underlying disease (infection, shock, trauma) contributes to the release of proteinases.

These disturbances may be harmful to the patient if the blood concentration or function of the most important proteinase inhibitors (α 1-proteinase inhibitor,α 2-macroglobulin) is reduced.

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


  1. 1.

    Aasen AO, Ohlsson K (1978) Release of granulocyte elastase in lethal canine endotoxin shock. Hoppe-Seylers Z Physiol Chem 359:683–690

  2. 2.

    Birkhan RH, Long CL, Fitkin D, Jeevanandam M, Blakemore WS (1981) Whole-body protein metabolism due to trauma in man as estimated by L-15N alanine. Am J Physiol 241:E64-E71

  3. 3.

    Blondin J, Janoff A (1976) The role of lysosomal elastase in the digestion ofEscherichia coli proteins by human polymorphonuclear leukocytes. J Clin Invest 58:971–979

  4. 4.

    Borgström A, Ohlsson K (1978) Studies on the turnover of endogenous cathodal trypsinogen in man. Eur J Clin Invest 8:379–382

  5. 5.

    Carp H, Janoff A (1979) In vitro suppression of serum elastase inhibitory capacity by reactive oxygen species generated by phagocytosing polymorphonuclear leukocytes. J Clin Invest 63:793–797

  6. 6.

    Cohen AB (1979) The effects in vivo and in vitro of oxidative damage to purified alpha1-antitrypsin and to the enzyme inhibiting activity of plasma. Am Rev Respir Dis 119:953–960

  7. 7.

    Conger JD, Hammond WS, Alfrey AC, Contiguglia SR, Huffer WE, Stanford RE (1975) Pulmonary calcification in chronic dialysis patients: Clinical and pathological studies. Am Intern Med 83:330–336

  8. 8.

    Craddock PR, Fehr J, Dalmasso AP, Brigham KL, Jacob HS (1977) Pulmonary vascular leukostasis resulting from complement activation by dialyzer cellophane membranes. J Clin Invest 59:879–888

  9. 9.

    Craddock PR, Hammerschmidt DE, White JG, Dalmasso AP, Jacobs HS (1977) Complement (C5a)-induced granulocyte aggregation in vitro. A possible mechanisms of complement-mediated leukostasis and leukopenia. J Clin Invest 60:260–265

  10. 10.

    Egbring R, Schmidt W, Fuchs G, Havemann K (1977) Demonstration of granulocyte proteases in plasma of patients with acute leukemia and septicemia with coagulation defects. Blood 49:219–231

  11. 11.

    Gerber ACh, Carson JH, Hadorn B (1974) Partial purification and characterization of a chymotrypsin-like enzyme from human neutrophil leukocytes. Biochim Biophys Acta 364:103–112

  12. 12.

    Goldberg AL, Kowit JD, Etlinger JD, Klemes Y (1978) Selective degradation of abnormal proteins in animal and bacterial cells. In: Segal HL, Doyle D (eds) Protein turnover and lysosome function. Academic Press, New York

  13. 13.

    Hällgren R, Venge P, Wilström B (1981) Hemodialysis-induced increase in serum lactoferrin and serum eosinophil cationic protein as signs of local neutrophil and eosinophil degranulation. Nephron 29:233–238

  14. 14.

    Havemann K, Gramse M, Gassel WD (1983) Cytochemical determination of granulocyte elastase and chymotrypsin in human myeloid cells and its application in acquired deficiency states and diagnosis of myeloid leukemia. Klin Wochenschr 61:49–56

  15. 15.

    Heidbreder E, Ralla W, Heidland A (1976) The exocrine pancreas in uremia: Clinical and experimental investigations. In: Heidland A, Hennemann H, Kult J (eds) Renal insufficiency. Thieme, Stuttgart, pp 230–240

  16. 16.

    Heidland A, Hörl WH, Heller N, Heine H, Neumann S, Heidbreder E (1983) Proteolytic enzymes and catabolism — enhanced release of granulocyte proteinases in uremic intoxication and during hemodialysis. Kidney Int, 1983

  17. 17.

    Hörl WH, Heidland A (1980) Enhanced proteolytic activity — cause of protein catabolism in acute renal failure. Am J Clin Nutr 33:1423–1427

  18. 18.

    Hörl WH, Jochum M, Heidland A, Fritz H (1983) Release of granulocyte proteinases during hemodialysis. Am J Nephrol 3:213–217

  19. 19.

    Hörl WH, Stepinski J, Gantert C, Hörl M, Heidland A (1981) Evidence for the participation of proteases on protein catabolism during hypercatabolic renal failure. Klin Wochenschr 59:751–759

  20. 20.

    Hörl WH, Stepinski J, Heidland A (1982) Further evidence for the participation of proteases in protein catabolism during hypercatabolic renal failure. In: Eliahou HE (ed) Acute renal failure. Libbey, London, pp 115–120

  21. 21.

    Janoff A, Blondin J, Sandhaus RA, Mosser A, Malemud CJ (1975) Human neutrophil elastase: in vitro effects on natural substrates suggest important physiological and pathological action. In: Reich E, Rifkin DB, Shaw E (eds) Proteases and biological control. Cold Spring Harbor Laboratory, Cold Spring Harbor, pp 603–630

  22. 22.

    Janoff A, Scherer J (1968) Mediators of inflammation in leukocyte lysosomes. IX. Elastinolytic activity in granules of human polymorphonuclear leukocytes. J Exp Med 128:1137–1155

  23. 23.

    Johnson D, Travis J (1978) Structural evidence for methionine at the reactive site of human α1-proteinase inhibitor. J Biol Chem 253:7142–7144

  24. 24.

    Kaplow LW, Goffinet JA (1968) Profound neutropenia during the early phase of hemodialysis. JAMA 203:1135–1137

  25. 25.

    Klessen C (1978) On testing the activity of proteases from human polymorphonuclear neutrophils on blood smear. J Histochem Cytochem 26:759–760

  26. 26.

    Klessen C, Tekolf W (1980) Cytochemical investigation of neutral proteases in polymorphonuclear (PMN) neutrophils in acute inflammatory diseases. Histochemistry 69:307–314

  27. 27.

    Lazarus GS, Daniels JR, Brown RS, Bladen HA, Fullmer HM (1968) Degradation of collagen by a human collagenolytic system. J Clin Invest 47:2622–2628

  28. 28.

    Long CL, Jeevanandam M, Kim BM, Kinney JM (1977) Whole-body protein synthesis and catabolism in septic man. Am J Clin Nutr 30:1340–1344

  29. 29.

    Morihara K, Tsuzuki H (1977) Production of protease and elastase by Pseudomonas aeruginosa strains isolated from patients. Infect Immun 15:679–685

  30. 30.

    Neumann S, Hennrich N, Gunzer G, Lang H (1983) Enzyme-linked immunoassay for human granulocyte elastase in complex with α1-proteinase inhibitor. In: Hörl WH, Heidland A (eds) Proteases: Potential role in health and disease. Plenum Press, New York London

  31. 31.

    Ohlsson K, Ohlsson J (1973) The neutral proteases of human granulocytes. Isolation and partial characterization of two granulocyte collagenases. Eur J Biochem 36:473–481

  32. 32.

    Richet G, Ardaillou R (1959) L'activité tripeptidasique due plasma au cours des affections severes contribution a l'étude de l'hypercatabolisms protidique. Presse Med 30:1229–1232

  33. 33.

    Riepe STP, Goldstein J, Alpers DH (1980) Effect of secreted Bacteroides proteases on human intestinal brush border hydrolases. J Clin Invest 66:314–322

  34. 34.

    Rindler R, Schmalzl F, Braunsteiner H (1974) Isolierung und Charakterisierung der chymotrypsinähnlichen Protease aus neutrophilen Granulozyten des Menschen. Schweiz Med Wochenschr 104:132–133

  35. 35.

    Schmidt W, Havemann K (1974) Isolation of elastase-like and chymotrypsin-like neutral proteases from human granulocytes. Hoppe-Seylers Z Physiol Chem 355:1077–1081

  36. 36.

    Smolen JE, Weissmann G (1978) The granulocyte: Metabolic properties and mechanisms of lysosomal enzyme release. In: Havemann K, Janoff A (eds) Neutral proteases of human polymorphonuclear leukocytes. Urban and Schwarzenberg, Baltimore Munich, pp 56–76

  37. 37.

    Tai JY, Kortt AA, Lia TY, Elliot SD (1976) Primary structure of streptococcal proteinases. III. Isolation of cynogen bromide peptides: complete covalent structure of the polypeptide chain. J Biol Chem 251:1955–1959

  38. 38.

    Wysocki H, Czarnecki R, Wierusz-Wysocka B, Wykretowicz A, Wysocki K, Baczyk K (1981) The selective polymorphonuclear mechanism of the hemodialysis (HD)-induced complement activation. Int J Artif Organs 4:174–177

Download references

Author information

Correspondence to Prof. A. A. Heidland.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Heidland, A., Hörl, W.H., Heller, N. et al. Granulocyte lysosomal factors and plasma elastase in uremia: A potential factor of catabolism. Klin Wochenschr 62, 218–224 (1984). https://doi.org/10.1007/BF01721047

Download citation

Key words

  • Granulocyte lysosomal factors
  • Elastase
  • Acute and chronic uremia
  • Catabolism