Proteases pp 1-20 | Cite as

Physiology and Pathophysiology of Neutral Proteinases of Human Granulocytes

  • Klaus Havemann
  • Margarethe Gramse
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 167)


The occurence of proteolytic enzymes in polymorphonuclear granulocytes was first demonstrated in 1888 by the famous clinician and biochemist Friedrich von Müller1 who showed that a glycerine extract of fresh pus digests fibrin or coagulated protein at a neutral or weakly alkaline pH. Later on at the end of the last and the beginning of this century further characterization of the enzymes including their serum antiproteases was achieved by German and American scientists2,3,4. However, the neutral proteases then became largely forgotten as the result of the attention paid to the acid-cathepsins of the rabbit leukocyte, a convenient but somewhat misleading cell.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    F. Müller, Apparently unpublished observations cited by: H. Kossel, “Beiträge zur Lehre vom Auswurf”, Zeitschrift Klin. Med., XIII: 149 (1888).Google Scholar
  2. 2.
    G. Jochmann und E. Müller, Über proteolytische Fermentwirkung der Leukozyten, Münchner Med. Wschr. 26 (1906).Google Scholar
  3. 3.
    G. Jochmann und E. Müller, Weitere Ergebnisse unserer Methode und Nachweis proteolytischer Fermentwirkung, Münchner Med. Wschr. 41 (1906).Google Scholar
  4. 4.
    E. L. Opie, Intracellular digestion: The enzymes and anti-enzymes concerned, Physiological Reviews 2: 522 1922.Google Scholar
  5. 5.
    A. Janoff, and J. Scherer, Mediators of inflammation in leukocyte lysosomes. IX. Elastinolytic activity in granules of human polymorphonuclear leukocytes, J. exp. Med. 128: 1137 1968.PubMedCrossRefGoogle Scholar
  6. 6.
    G. S. Lazarus, J. R. Daniels, R.S. Braun, H. A. Bladen, and H. M. Fullmer, Degradation of collagen by a human granulocyte collagenolytic system, J. Clin. Invest. 47: 2622 1968.PubMedCrossRefGoogle Scholar
  7. 7.
    W. Schmidt, and K. Havemann, Isolation of elastase-like and chymotrypsin-like neutral proteases from human granulocytes, Hoppe-Seyler’s Z. Physiol. Chem. 355: 1077 1974.PubMedCrossRefGoogle Scholar
  8. 8.
    A. C. Gerber, J. H. Carson, and B. Hadorn, Partial purification and characterization of a chymotrypsin-like enzyme from human neutrophil leukocytes, Biochim. Biophys. Acta 364: 103 1974.PubMedCrossRefGoogle Scholar
  9. 9.
    R. Rindler, F. Schmalzl und H. Braunsteiner, Isolierung und Charakterisierung der chymotrypsinähnlichen Protease aus neutrophilen Granulozyten des Menschen, Schweiz. Med. Wschr. 104: 132 1974.PubMedGoogle Scholar
  10. 10.
    K. Ohlsson, and I. Olsson, The neutral proteases of human granulocytes. Isolation and partial characterization of granulocyte elastases, Eur. J. Biochem. 42: 519 1974.PubMedCrossRefGoogle Scholar
  11. 11.
    K. Ohlsson, and I. Olsson, The neutral proteases of human granulocytes. Isolation and partial characterization of two granulocyte collagenases, Eur. J. Biochem. 36: 473 1973.PubMedCrossRefGoogle Scholar
  12. 12.
    B. Dewald, R. Rindler-Ludwig, U. Bretz, and M. Baggiolini, Sub-cellular localization and heterogeneity of neutral proteases in neutrophilic polymorphonuclear leukocytes, J. exp. Med. 141: 709 1975.PubMedCrossRefGoogle Scholar
  13. 13.
    K. Ohlsson, J. Ohlsson, and J. K. Spitznagel, Localization of chymotrypsin-like cationic protein, collagenase and elastase in azurophil granules of human neutrophilic polymorphonuclear leukocytes, Hoppe-Seyler’s Z. Physiol. Chem. 358: 361 1977.PubMedCrossRefGoogle Scholar
  14. 14.
    B. Dewald, U. Bretz, and M. Baggiolini, Release of gelatinase from a novel secretory compartment of human neutrophils, J. Clin. Invest. 70: 518 1982.PubMedCrossRefGoogle Scholar
  15. 15.
    J. Ohlsson, The intracellular transport of glycosaminoglycans in human leukocytes, Exp. Cell. Res. 54: 318 1969.CrossRefGoogle Scholar
  16. 16.
    D. F. Bainton, J. L. Ullyot, and M. G. Farquhar, The development of neutrophilic polymorphonuclear leukocytes in bone marrow, J. exp. Med. 134: 907 1971.PubMedCrossRefGoogle Scholar
  17. 17.
    J. M. Clark, B. M. Aiken, D. W. Vaughan, and H. M. Kagan, Ultrastructural localization of elastase-like enzymes in human neutrophils, J. Histochem. Cytochem. 28: 90 1980.PubMedCrossRefGoogle Scholar
  18. 18.
    J. Poensgen, G. Adler, M. Gramse, and K. Havemann, Phagocytosis and enzyme release from stimulated neutrophils, (Abstract), Blut 45: 177 1982.Google Scholar
  19. 19.
    K. Havemann, M. Gramse, and W. D. Gassel, Cytochemical determination of granulocyte elastase and chymotrypsin in human myeloid cells and its application in aquired deficiency states and diagnosis of myeloid leukemia, Klin. Wschr. 61: 49 1983.PubMedCrossRefGoogle Scholar
  20. 20.
    K. Havemann, and A. Janoff, Neutral proteases of human polymorphonuclear leukocytes, eds. Urban & Schwarzenberg, Baltimore-München (1978).Google Scholar
  21. 21.
    C. J. Malemud, and A. Janoff, Identification of neutral proteases in human neutrophil granules that degrade articular cartilage proteoglycan, Arthritis Rheum. 18: 361 (1975).PubMedCrossRefGoogle Scholar
  22. 22.
    A. Janoff, At least three human neutrophil lysosomal proteases are capable of degrading joint connective tissue, Ann. NY Acad. Sci. 256: 402 1976.CrossRefGoogle Scholar
  23. 23.
    K. Ohlsson, Purification and properties of granulocyte collagenase and elastase, in: “Neutral Proteases ...” (ref. 20), p. 89 (1978).Google Scholar
  24. 24.
    W. Schmidt, R. Egbring, and K. Havemann, Effect of elastase-like and chymotrypsin-like neutral proteases from human granulocytes on isolated clotting factors, Thromb. Res. 6: 315 1975.PubMedCrossRefGoogle Scholar
  25. 25.
    J. A. McDonald, and D. G. Kelley, Degradation of fibronectin by leukocyte elastase, J. Biol. Chem. 255: 8848 1980.PubMedGoogle Scholar
  26. 26.
    T. Vartio, H. Seppä, and A. Vaheri, Susceptibility of soluble and matrix fibronectins to degradation by tissue proteinases, mast cell chymase and cathepsin G, J. Biol. Chem. 256: 471 1981.Google Scholar
  27. 27.
    P. M. Starkey, A. J. Barrett, and M. C. Burleigh, The degradation of articular collagen by neutrophil proteinases, Biochim. Biophys. Acta 483: 386 1977.PubMedCrossRefGoogle Scholar
  28. 28.
    J. E. Gadek, G. A. Fells, D. G. Wright, and R. G. Crystal, Human neutrophil elastase functions as a type III collagen collagenase, Biochem. Biophys. Res. Com. 95: 1815 1981.CrossRefGoogle Scholar
  29. 29.
    C. L. Mainardi, S. N. Dixit, and A. H. Kany, Degradation of type IV (basement membrane) collagen by a proteinase isolated from human polymorphonuclear leukocyte granules, J. Biol. Chem. 255: 5435 1980.PubMedGoogle Scholar
  30. 30.
    M. Davies, A. J. Barrett, J. Travis, E. Sanders, and G. A. Coles, The degradation of human glomerular basement membrane with purified lysosomal proteinases: Evidence for the pathogenic role of the polymorphonuclear leukocyte in glomerulonephritis, Clin. Sci. Mol. Med. 54: 233 1978.PubMedGoogle Scholar
  31. 31.
    P. Henriksson, I. M. Nilsson, K. Ohlsson, and P. Stenberg, Granulocyte elastase activation and degradation of factor XIII, Thromb. Res. 18: 343 1980.PubMedCrossRefGoogle Scholar
  32. 32.
    M. Jochum, S. Lander, N. Heimburger, and H. Fritz, Effect of human granulocyte elastase on isolated human antithrombin III, Hoppe-Seyler’s Z. Physiol. Chem. 362: 103 1981.PubMedCrossRefGoogle Scholar
  33. 33.
    H. G. Klingemann, R. Egbring, M. Holst, M. Gramse, and K. Havemann, Digestion of α2-plasmin inhibitor by neutral proteases from human leukocytes, Thromb. Res. 24: 479 1981.PubMedCrossRefGoogle Scholar
  34. 34.
    M. S. Brower, and P. C. Harpel, Proteolytic cleavage and inactivation of α2-plasmin inhibitor and C1 inactivator by human polymorphonuclear leukocyte elastase, J. Biol. Chem. 257: 9849 1982.PubMedGoogle Scholar
  35. 35.
    P. Venge, and J. Olsson, Cationic proteins of human granulocytes VI. Effect on the complement system and mediation of chemotactic activity, J. Immunol. 115: 1505 (1975).PubMedGoogle Scholar
  36. 36.
    P. Venge, Polymorphonuclear leukocyte proteases and their effects on complement components and neutrophil function, in: “Neutral Proteases ...” (ref. 20), p.264 (1978).Google Scholar
  37. 37.
    J. C. Taylor, I. P. Crawford, and T. E. Hugli, Limited degradation of the third component (C3) of human complement by human leukocyte elastase (HLE): Partial characterization of C3 fragments, Biochemistry 16: 3390 1977.PubMedCrossRefGoogle Scholar
  38. 38.
    F. W. Orr, J. Varani, D. L. Kreutzer, R. M. Senior, and D. A. Ward, Digestion of the fifth component of complement by leukocyte enzymes, Am. J. Pathol. 94: 75 1979.PubMedGoogle Scholar
  39. 39.
    U. Johnsson, K. Ohlsson, and I. Olsson, Effects of granulocyte neutral proteases on complement components, Scand. J. Immunol. 5: 421 (1976).CrossRefGoogle Scholar
  40. 40.
    C. Löffler, Human granulocyte elastase and chymotrypsin. Generation of chemotactic activity in the presence of serum antiproteases, in: “Neutral proteases ...” (ref. 20), p. 292 (1978).Google Scholar
  41. 41.
    U. Hadding, C. Löffler, M. Gramse and K. Havemann, Influence of elastase-like protease on guinea pig C3, factor B of the properdin system and the tumor cell line EL 4, in “Neutral Proteases ...” (ref. 20), p. 287 (1978).Google Scholar
  42. 42.
    A. Solomon, W. Schmidt, and K. Havemann, Bence Jones Proteins and light chains of immunoglobulins. XIII. Effect of elastase-like and chymotrypsin-like neutral proteases derived from human granulocyte s on Bence Jones Proteins, J. Immunol. 117: 1010 1976.PubMedGoogle Scholar
  43. 43.
    A. Solomon, M. Gramse, and K. Havemann, Proteolytic cleavage of IgG molecules by neutral proteases of polymorphonuclear leukocytes, Eur. J. Immunol. 8: 782 1978.PubMedCrossRefGoogle Scholar
  44. 44.
    J. D. Folds, H. E. Prince, and J. K. Spitznagel, Limited cleavage of human immunoglobulins by elastase of human neutrophil polymorphonuclear granulocytes, Lab. Invest. 39: 313 1978.PubMedGoogle Scholar
  45. 45.
    A. Baici, M. Knöpfel, K. Fehr, and A. Böni, Cleavage of human IgM with human lysosomal elastase, Immunol. Letters 2: 47 1980.CrossRefGoogle Scholar
  46. 46.
    H. E. Prince, J. D. Folds, and J. K. Spitznagel, Interaction of human polymorphonuclear leukocyte (PMN) elastase with human IgM. Production of a factor enhancing PMN migration in vitro, Immunol. Commun. 9: 23 1980.PubMedGoogle Scholar
  47. 47.
    G. Kolb, H. Köppler, M. Gramse, and K. Havemann, Cleavage of IgG by elastase-like protease (ELP) of human polymorphonuclear leukocytes: Isolation and characterization of Fab and Fc fragments and low-molecular-weight peptides. Stimulation of granulocyte function by ELP-derived Fab and Fc fragments, Immunobiology 161: 507 1982.PubMedCrossRefGoogle Scholar
  48. 48.
    H. Fritz, Failure to detect intrinsic kininogenase activity in PMN elastase, in: “Neutral Protease ...” (ref. 20), p. 261 (1978).Google Scholar
  49. 49.
    G. Murphy, U. Bretz, M. Baggiolini, and J. J. Reynolds, The latent collagenase and gelatinase of human polymorphonuclear neutrophil leukocytes, Biochem. J. 192: 517 1980.PubMedGoogle Scholar
  50. 50.
    H. W. Macartney, and H. Tschesche, Latent collagenase from human polymorphonuclear leukocytes and activation to collagenase by removal of an inhibitor, FEBS Letters 119: 327 1980.PubMedCrossRefGoogle Scholar
  51. 51.
    M. G. Tonnesen, M. S. Klempner, K. F. Austen, and B. U. Wintroub, Identification of a human neutrophil angiotensin II-generating protease as cathepsin G, J. Clin. Invest. 69: 25 1982.PubMedCrossRefGoogle Scholar
  52. 52.
    K. Ohlsson and M. Delshammer, Interactions between granulocyte elastase and collagenase and the plasma proteinase inhibitors in vitro and in vivo, in: “Dynamics of Connective Tissue Macromolecules,” P. M. C. Burleigh, A. R. Poole, eds., North-Holland Publishing Company (1975).Google Scholar
  53. 53.
    H. Tegner, and K. Ohlsson, Localization of a low-molecular-weight protease inhibitor to tracheal and maxillary sinus mucosa, Hoppe-Seyler’s Z. Physiol. Chem. 358: 425 1977.PubMedCrossRefGoogle Scholar
  54. 54.
    H. Schiessler, M. Arnhold, K. Ohlsson, and H. Fritz, Inhibitors of acrosin and granulocyte proteinases from human genital tract secretions, Hoppe-Seyler’s Z. Physiol. Chem. 357: 1251 1976.PubMedCrossRefGoogle Scholar
  55. 55.
    M. E. Englert, M. J. Landes, J. E. Birnbaum, A. L. Oronsky, and S. S. Kerwar, Studies on a leukocyte elastase inhibitor present in the culture medium of inflamed synovial tissue, Biochem. Biophys. Res. Commun. 96: 498 1980.PubMedCrossRefGoogle Scholar
  56. 56.
    P. C. Harpel, and M. W. Mosesson, Degradation of human fibrinogen by plasma α2 macroglobulin-enzyme complexes, J. Clin. Invest. 52: 2175 1973.PubMedCrossRefGoogle Scholar
  57. 57.
    P. Venge, I. Olsson, and H. Odeberg, Cationic proteins of human granulocytes. V. Interaction with plasma protease inhibitors, Scand. J. Clin. Lab. Invest. 35: 737 1975.PubMedCrossRefGoogle Scholar
  58. 58.
    K. Ohlsson, and C. B. Laurell, The disappearance of enzyme-inhibitor complexes from the circulation of man, Clin. Sci. Mol. Med. 51: 87 1976.PubMedGoogle Scholar
  59. 59.
    K. Ohlsson, and H. Tegner, Granulocyte elastase and plasma protease inhibitors in purulent sputum, Europ. J. Clin. Invest. 5: 221 1975.PubMedGoogle Scholar
  60. 60.
    J. Saklatvala, and A. J. Barrett, Identification of proteinases in rheumatoid synovium. Detection of leukocyte elastase, cathepsin G, and another serine proteinase, Biochim. Biophys. Acta 615: 167 1980.PubMedCrossRefGoogle Scholar
  61. 61.
    C. T. Lee, A. M. Fein, M. Lippmann, H. Holtzmann, P. Rumbel, and G. Weinbaum, Elastolytic activity in pulmonary lavage fluid from patients with adult respiratory-distress syndrome, New Engl. J. Med. 304: 192 1981.PubMedCrossRefGoogle Scholar
  62. 62.
    N. R. Matheson, P. W. Wong, and J. Travis, Enzymatic inactivation of human α1proteinase inhibitor by neutrophil myeloperoxidase, Biochem. Biophys. Res. Commun. 88: 402 1979.PubMedCrossRefGoogle Scholar
  63. 63.
    A. B. Cohen, The effect in vivo and in vitro of oxidative damage to purified α1 antitrypsin and to the enzyme inhibiting activity of plasma, Am. Rev. Respir. Dis. 119: 953 1979.PubMedGoogle Scholar
  64. 64.
    P. M. Henson, The immunologic release of constituents from neutrophil leukocytes. I. The role of antibody and complement on nonphagocytosable surfaces or phagocytosable particles, J. Immunol. 107: 1535 1971.PubMedGoogle Scholar
  65. 65.
    G. Weissmann, R. B. Zurier, P. J. Spieler, and J. M. Goldstein, Mechanisms of lysosomal enzyme release from leukocyte exposed to immune complexes and other particles, J. exp. Med. 134: 1495 1971.Google Scholar
  66. 66.
    I. Olsson, T. Olofsson, P. Venge, and I. Winquist, Release of biologically active compounds from neutrophil and eosinophil leukocyte granules, Monographs in Allergy 17: 130 1981.Google Scholar
  67. 67.
    G. Weissmann, J. E. Smolen, and H. M. Korchak, Release of inflammatory mediators from stimulated neutrophils, New Engl. J. Med. 303: 27 1980.PubMedCrossRefGoogle Scholar
  68. 68.
    W. Schmidt, Differential release of elastase and chymotrypsin from polymorphonuclear leukocytes, in “Neutral Proteases...,” (ref. 20), p.77 (1978).Google Scholar
  69. 69.
    I. Goldstein, S. Hoffstein, J. Gallin, and G. Weissmann, Mechanisms of lysosomal enzyme release from human leukocytes: Microtubule assembly and membrane fusion induced by a component of complement, Proc. Nat. Acad. Sci. (Wash.) 70: 2916 (1973).Google Scholar
  70. 70.
    H. J. Showell, R.J. Freer, S.H. Zigmond, E. Schiffmann, S. Aswanikumar, B. Corcoran, E.L. Becker, The structure-activity-relations of synthetic peptides as chemotactic factors and inducers of lysosomal enzyme secretion for neutrophils, J. exp. Med. 143: 1154 1976.PubMedCrossRefGoogle Scholar
  71. 71.
    A. B. Kay, D. S. Pepper, and R. McKenzie, The identification of fibrinopeptide B as a chemotactic agent derived from human fibrinogen, Brit. J. Haemotol. 27: 669 1974.CrossRefGoogle Scholar
  72. 72.
    M. Tonnesen, Personal communication (C5a attachment) (1982).Google Scholar
  73. 73.
    I. I. Gigli, and R.A. Nelson, Complement dependent immune phagocytosis. I. Requirements for Cl, C4, C2, C3, Exp. Cell Res. 51: 45 1968.PubMedCrossRefGoogle Scholar
  74. 74.
    R. Hallgren, and P. Venge, Cationic proteins of human granulocytes: Enhancement of phagocytosis by staphylococcus protein A-IgG complexes, Inflammation 1: 237 1976.CrossRefGoogle Scholar
  75. 75.
    M. E. Schmidt, S. D. Douglas, P. Quie, R. D. Nelson, W. Schmidt, and K. Havemann, Effect of neutral granulocyte proteases on human immunocompetent cells: Action of elastase-like protease and chymotrypsin-like protease on mononuclear phagocytes, in: “Neutral proteases...,” (ref. 20), p. 298 (1978).Google Scholar
  76. 76.
    E. F. Plow, and T. S. Edgington, An alternative pathway for fibrinolysis. I. The cleavage of fibrinogen by leukocytic proteases at physiologic pH, J. Clin. Invest. 56: 30 1975.PubMedCrossRefGoogle Scholar
  77. 77.
    M. Gramse, C. Bingenheimer, W. Schmidt, R. Egbring, and K. Havemann, Degradation products of fibrinogen by elastase-like neutral protease from human granulocytes. Characterization and effects on blood coagulation in vitro, J. Clin. Invest. 61: 1027 1978.PubMedCrossRefGoogle Scholar
  78. 78.
    K. Havemann, W. Schmidt, U. Bogdanm, and M. Gramse, Effect of polymorphonuclear granulocyte proteases on immunocompetent cells, in: “Neutral Proteases...,” (ref. 20), p. 306 (1978).Google Scholar
  79. 79.
    K. Ky, and M. Ziff, Enhancement of in vitro immunoglobulin synthesis of human lymphocytes by lysosomal enzymes from polymorphonuclear leukocytes, Clin. exp. Immunol. 27: 254 1977.Google Scholar
  80. 80.
    R. Hallgren, and P. Venge, Cationic proteins of human granulocytes. Effects on human platelet aggregation and serotonine release, Inflammation. 1: 359 1976.CrossRefGoogle Scholar
  81. 81.
    T. J. Williams, Personal communication (1982).Google Scholar
  82. 82.
    G. Camussi, J. M. Menzia-Huerta, and J. Benveniste, Release of platelet activating factor and histamine, I. Effect of immune complexes, complement and neutrophils on human and rabbit mastocytes and basophils, Immunology 33: 523 1978.Google Scholar
  83. 83.
    R. Egbring, W. Schmidt, G. Fuchs, and K. Havemann, Demonstration of granulocyte proteases in plasma of patients with acute leukemia and septicemia with coagulation defects, Blood 49: 219 1977.PubMedGoogle Scholar
  84. 84.
    P. M. Neame, J. G. Kelton, J. R. Walker, I. O. Stewart, H. L. Nossel, and J. Hirsh, Thrombocytopenia in septicemia: the role of disseminated intravascular coagulation, Blood 56: 88 1980.PubMedGoogle Scholar
  85. 85.
    C. Merskey, Defibrination syndrome or...? Blood 41: 599 1973.PubMedGoogle Scholar
  86. 86.
    K. H. Duswald, M. Jochum und H. Fritz, Neue Erkenntnisse zur Pathobiochemie der Sepsis nach abdominal-chirurgischen Operationen, in.: “Chirurgisches Forum 82 für experimentelle und klinische Forschung,” S. Weller, ed., Springer (1982).Google Scholar
  87. 87.
    R. Egbring and K. Havemann, Possible role of polymorphonuclear granulocyte proteases in blood coagulation, in: “Neutral Proteases...” (ref. 20), p. 442 (1978).Google Scholar
  88. 88.
    P. R. Craddock, D. Hammerschmidt, J. G. White, A. P. Dalmasso, and H. S. Jacob, Complement (C5a) induced granulocyte aggregation in vitro, J. Clin. Invest. 60: 260 1977.PubMedCrossRefGoogle Scholar
  89. 89.
    P. R. Craddock, J. Fehr, A. P. Dalmasso, K. L. Brigham, and H. S. Jacob, Hemodialysis leukopenia and pulmonary vascular leukostasis resulting from complement activation by dialyzer cellophane membranes, J. Clin. Invest. 59: 879 1977.PubMedCrossRefGoogle Scholar
  90. 90.
    C. G. Cochrane, and B. A. Aikin, Polymorphonuclear leukocytes in immunologic reactions: The destruction of vascular basement membrane in vivo and in vitro, J. exp. Med. 124: 733 1966.PubMedCrossRefGoogle Scholar
  91. 91.
    A. Janoff, Mediators of tissue damage in leukocyte lysosomes X. Further studies on human granulocyte elastase, Lab. Invest. 22: 228 1970.PubMedGoogle Scholar
  92. 92.
    A. Janoff, R. A. Sandhaus, V. D. Hospelhorn, and R. Rosenberg, Digestion of lung proteins by human leukocyte granules in vitro, Proc. Soc. Exp. Biol. Med. 140: 516 1972.PubMedGoogle Scholar
  93. 93.
    M. Galdstone, A. L. Davis, and A. Janoff, Familial variation of leukocyte lysosomal protease and serum α1antitrypsin as determinants in chronic obstructive pulmonary disease, Am. J. Resp. Dis. 108: 1020 1974.Google Scholar
  94. 94.
    A. Janoff, and A. Carp, Possible mechanism of emphysema in cigarette smokers: Cigarette smoke condensate suppresses proteinase inhibitors in vitro, Am. Rev. Resp. Dis. 116: 65 1977.PubMedGoogle Scholar
  95. 95.
    A. L. Oronsky, L. Ignarro, and R. J. Perper, Release of cartilage mucopolysaccharide-degrading neutral protease from human leukocytes, J. exp. Med. 138: 461 1972.CrossRefGoogle Scholar
  96. 96.
    R. A. Turner, G. B. Counts, W. J. Treadway, D. A. Holt, and C. A. Agudelo, Rheumatoid factor and monosodium urate crystalneutrophil interactions in gouty inflammation, Inflammation 5: 353 1982.CrossRefGoogle Scholar
  97. 97.
    E. Sanders, G. A. Coles, and M. Davies, Lysosomal enzymes in human urine: Evidence for polymorphonuclear leukocyte proteinase involvement in the pathogenesis of human glomerulonephritis, Clin. Sci. Mol. Med. 54: 667 1978.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Klaus Havemann
    • 1
  • Margarethe Gramse
    • 1
  1. 1.Department of HematologyUniversity of MarburgGermany

Personalised recommendations