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The polymorphonuclear leukocyte

  • Immunosuppression and Inflammation
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Abstract

Polymorphonuclear leukocytes (PMNs) are one of the main sources of enzymes responsible for tissue damage in inflammatory processes. These enzymes are stored in two types of cytoplasmic granules. Azurophil granules contain lysosomal hydrolases, neutral serine proteinases, and bactericidal elements (myeloperoxidase and lysozyme). Specific granules contain collagenase, lysozyme and lactoferrin but lack lysosomal hydrolases. PMNs store all four classes of tissue proteinases, carboxyl, thiol and serine proteinases in the azurophil granules, and metallo proteinases in the specific granules. Three serine proteinases have been identified, elastase, cathepsin G and a third enzyme, which together account for a large proportion of the protein of the azurophil granules. In the course of phagocytic events, all these enzymes are released extracellularly. The neutral proteinases degrade proteoglycans and collagen. In vitro, they stimulate B-lymphocytes, which suggests that they may have immuno-potentiating activity when they are released at sites of chronic inflammation.

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References

  1. D.F. Bainton andM.G. Farquhar,Origin of Granules in Polymorphonuclear Leukocytes: Two Types Derived from Opposite Faces of the Golgi Complex in Developing Granulocytes, J. Cell Biol.28, 277–301 (1966).

    Google Scholar 

  2. B.K. Wetzel, R.G. Horn andS.S. Spicer,Fine Structural Studies on the Development of Heterophil, Eosinophil, and Basophil Granulocytes in Rabbit, Lab. Invest.16, 349–382 (1967).

    Google Scholar 

  3. D.F. Bainton, J.L. Ullyot andM.G. Farquhar,The Development of Neutrophilic Polymorphonuclear Leukocytes in Human Bone Marrow, J. exp. Med.134, 907–934 (1971).

    Google Scholar 

  4. Z.A. Cohn andJ.G. Hirsch,The Isolation and Properties of the Specific Cytoplasmic Granules of Rabbit Polymorphonuclear Leukocytes, J. exp. Med.112, 983–1004 (1960).

    Google Scholar 

  5. Z.A. Cohn andJ.G. Hirsch,The Influence of Phagocytosis on the Intracellular Distribution of Granule Associated Components of Polymorphonuclear Leukocytes, J. exp. Med.112, 1015–1023 (1960).

    Google Scholar 

  6. J.G. Hirsch andZ.A. Cohn,Degranulation of Polymorphonuclear Leukocytes Following Phagocytosis of Microorganisms, J. exp. Med.112, 1005–1014 (1960).

    Google Scholar 

  7. D. Zucker-Franklin andJ.G. Hirsch,Electron Microscope Studies on the Degranulation of Rabbit Peritoneal Leukocytes During Phagocytosis, J. exp. Med.120, 569–575 (1964).

    Google Scholar 

  8. M. Baggiolini, J.G. Hirsch andC. de Duve,Resolution of Granules from Rabbit Heterophil Leukocytes into Distinct Populations by Zonal Sedimentation, J. Cell Biol.40, 529–541 (1969).

    Google Scholar 

  9. M. Baggiolini, J.G. Hirsch andC. de Duve,Further Biochemical and Morphological Studies of Granule Fractions from Rabbit Heterophil Leukocytes, J. Cell Biol.45, 586–597 (1970).

    Google Scholar 

  10. M. Baggiolini, C. de Duve, P.L. Masson andJ.F. Heremans,Association of Lactoferrin with Specific Granules in Rabbit Heterophil Leukocytes, J. exp. Med.131, 559–570 (1970).

    Google Scholar 

  11. M. Baggiolini,The Isolation of Granules from Neutrophil Polymorphonuclear Leukocytes (PMN's), Meth. Enzym.31, 345–353 (1974).

    Google Scholar 

  12. M. Baggiolini, U. Bretz, M. Schneider andE. Tellenbach,Isopycnic Centrifugation Under Low Hydrostatic Pressure. A Novel Connecting Unit for Manual Operation of Beaufay's Rotor, Anal. Biochem.77, 503–512 (1977).

    Google Scholar 

  13. M. Baggiolini, U. Bretz andB. Gusus,Biochemical Characterization of Azurophil and Specific Granules from Human and Rabbit Polymorphonuclear Leukocytes, Schweiz. med. Wschr.104, 129–132 (1974).

    Google Scholar 

  14. M.S. Leffell andJ.K. Spitznagel,Association of Lactoferrin with Lysozyme in Granules of Human Polymorphonuclear Leukocytes, Infect. Immun.6, 761–765 (1972).

    Google Scholar 

  15. U. Bretz andM. Baggiolini,Biochemical and Morphological Characterization of Azurophil and Specific Granules of Human Neutrophilic Polymorphonuclear Leukocytes, J. Cell Biol.63, 251–269 (1974).

    Google Scholar 

  16. J.K. Spitznagel, F.G. Dalldorf, M.S. Leffell, J.D. Folds, I.R.H. Welsh, M.H. Cooney andL.E. Martin,Character of Azurophil and Specific Granules Purified from Human Polymorphonuclear Leukocytes, Lab. Invest.30, 774–785 (1974).

    Google Scholar 

  17. B. Dewald, R. Rindler-Ludwig, U. Bretz andM. Baggiolini,Subcellular Localization and Heterogeneity of Neutral Proteases in Neutrophilic Polymorphonuclear Leukocytes, J. exp. Med.141, 709–723 (1975).

    Google Scholar 

  18. G. Murphy, J.J. Reynolds, U. Bretz andM. Baggiolini,Collagenase is a Component of the Specific Granules of Human Neutrophil Leukocytes, Biochem. J.162, 195–197 (1977).

    Google Scholar 

  19. M. Baggiolini,The Enzymes of the Granules of Polymorphonuclear Leukocytes and their Functions, Enzyme13, 132–160 (1972).

    Google Scholar 

  20. J.L. Avila andJ. Convit,Studies on Human Polymorphonuclear Leukocyte Enzymes. I. Assay of Acid hydrolases and Other Enzymes, Biochim. Biophys. Acta293, 397–408 (1973).

    Google Scholar 

  21. P. Davies, A.C. Allison andW.J. Hylton,The Identification, Properties and Subcellular Distribution of Cathepsins B1 and C (Dipeptidyl Amino-Peptidase I) in Human Peripheral-Blood Leucocytes, Biochem. Soc. Trans.2, 432–434 (1974).

    Google Scholar 

  22. S.P. Kane andT.J. Peters,Analytical Subcellular Fractionation of Human Granulocytes with Reference to the Localization of Vitamin B 12-Binding Proteins, Clin. Sci. Mol. Med.49, 171–182 (1975).

    Google Scholar 

  23. U. Bretz andM. Baggiolini,Association of the Alkaline Phosphatase of Rabbit Polymorphonuclear Leukocytes with the Membrane of the Specific Granules, J. Cell Biol.59, 696–707 (1973).

    Google Scholar 

  24. R.H. Michell, M.J. Karnovsky andM.L. Karnovsky,The Distribution of Some Granule-Associated Enzymes in Guinea-Pig Polymorphonuclear Leukocytes, Biochem. J.116, 207–216 (1970).

    Google Scholar 

  25. H. Ohta,A Biochemical Study on the Neutrophilic Granules Isolated in a Pure State from Leukocyte Homogenate, Acta haematol. jap.27, 555–565 (1964).

    Google Scholar 

  26. D. Hegner,Isolierung und Enzymbestand von Granula aus polymorphkernigen Leukozyten des peripheren Rinderblutes, Physiol. Chem.349, 544–554 (1968).

    Google Scholar 

  27. K. Brune andJ.K. Spitznagel,Peroxidaseless Chicken Leukocytes: Isolation and Characterization of Antibacterial Granules, J. Infect. Dis.127, 84–94 (1973).

    Google Scholar 

  28. P.G. Rausch andP.G. Canonico,Characterization of Monkey Peripheral Neutrophil Granules During Infection, Inf. Immun.12, 687–693 (1975).

    Google Scholar 

  29. H.I. Zeya andJ.K. Spitznagel,Characterization of Cationic Protein-Bearing Granules of Polymorphonuclear Leukocytes, Lab. Invest.24, 229–236 (1971).

    Google Scholar 

  30. A. Janoff andJ. Scherer,Mediators of Inflammation in Leukocyte Lysosomes. IX. Elastinolytic Activity in Granules of Human Polymorphonuclear Leukocytes, J. exp. Med.128, 1137–1155 (1968).

    Google Scholar 

  31. A. Janoff,Purification of Human Granulocyte Elastase by Affinity Chromatography, Lab. Invest.29, 458–464 (1973).

    Google Scholar 

  32. K. Ohlsson andI. Olsson,The Neutral Proteases of Human Granulocytes. Isolation and Partial Characterization of Two Granulocyte Collagenases, Eur. J. Biochem.36, 473–481 (1973).

    Google Scholar 

  33. R. Rindler-Ludwig andH. Braunsteiner,Cationic Proteins from Human Neutrophil Granulocytes. Evidence for their Chymotrypsin-like Properties, Biochim. Biophys. Acta379, 606–617 (1975).

    Google Scholar 

  34. Ph.M. Starkey andA.J. Barrett,Human Lysosomal Elastase. Catalytic and Immunological Properties, Biochem. J.155, 265–271 (1976).

    Google Scholar 

  35. Ph.M. Starkey andA.J. Barrett,Human Cathepsin G. Catalytic and Immunological Properties, Biochem. J.155, 273–278 (1976).

    Google Scholar 

  36. R. Rindler-Ludwig, F. Schmalzl andH. Braunsteiner,Esterases in Human Neutrophil Granulocytes: Evidence for their Protease Nature, Brit. J. Haematol.27, 57–64 (1974).

    Google Scholar 

  37. M.C. Burleigh, A.J. Barrett andG.S. Lazarus,Cathepsin B1. A Lysosomal Enzyme that Degrades Native Collagen, Biochem. J.137, 387–398 (1974).

    Google Scholar 

  38. U. Bretz andM. Baggiolini,Subcellular Localization of Specific Collagenase in Human Polymorphonuclear Leukocytes. Submitted for publication, 1977.

  39. A.J. Barrett,The Enzymic Degradation of Cartilage Matrix, in:Dynamics of Connective Tissue Macromolecules (Eds. P.M.C. Burleigh and A.R. Poole; North-Holland Publishing Co., Amsterdam, 1975), pp. 189–226.

    Google Scholar 

  40. A.J. Barrett andPh.M. Starkey,The Possible Role of Leucocyte Proteinases in the Tissue Damage of Rheumatoid Arthritis, in:Rheumatoid Arthritis (Eds. J.L. Gordon and B.L. Hazleman; Elsevier/North Holland Biomedical Press, Amsterdam, 1977), pp. 211–221.

    Google Scholar 

  41. M. Ziff, H.J. Gribetz andJ. LoSpalluto,Effect of Leukocyte and Synovial Membrane Extracts on Cartilage Mucoprotein, J. Clin. Invest.39, 405–412 (1960).

    Google Scholar 

  42. G. Weissmann andI. Spilberg,Breakdown of Cartilage Protein-Polysaccharide by Lysosomes, Arthritis Rheumat.,11, 5895–5902 (1968).

    Google Scholar 

  43. L. Ignarro, A. Oronsky andR.J. Perper,Breakdown of Noncollagenous Chondromucoprotein Matrix by Leukocyte Lysosome Granule Lysates from Guinea Pig, Rabbit and Human, Clin. Immunol. Immunopathol.2, 36–51 (1973).

    Google Scholar 

  44. A. Oronsky, L. Ignarro andR.J. Perper,Release of Cartilage Mucopolysaccharide-Degrading Neutral Protease from Human Leukocytes, J. exp. Med.138, 461–472 (1973).

    Google Scholar 

  45. A. Janoff, G. Feinstein, Ch.J. Malemud andJ.M. Elias,Degradation of Cartilage Proteoglycan by Human Leukocyte Granule Neutral Proteases — A Model of Joint Injury. I. Penetration of Enzyme into Rabbit Articular Cartilage and Release of 35 SO 4-Labeled Material from the Tissue, J. Clin. Invest.57, 615–624 (1976).

    Google Scholar 

  46. H. Keiser, R.A. Greenwald, G. Feinstein andA. Janoff,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.57, 625–632 (1976).

    Google Scholar 

  47. A.J. Barrett,The Possible Role of Leucocyte Proteinases in Damage to Articular Cartilage. This issue.

  48. T.L. Vischer, U. Bretz andM. Baggiolini,In vitro Stimulation of Lymphocytes by Neutral Proteinases from Human Polymorphonuclear Leukocyte Granules, J. exp. Med.144, 863–870 (1976).

    Google Scholar 

  49. T.L. Vischer,Stimulation of Mouse B Lymphocytes by Trypsin, J. Immunol.113, 58–62 (1974).

    Google Scholar 

  50. J.G. Kaplan andC. Bona,Proteases as Mitogens, Exp. Cell Res.88, 388–394 (1974).

    Google Scholar 

  51. T.L. Vischer andL. Bertrand,Stimulating Effect of Neutral Proteinases on Cells in vitro, Agents and Actions6, 180–182 (1976).

    Google Scholar 

  52. G. Poste andA.C. Allison,Membrane Fusion, Biochim. Biophys. Acta300, 421–465 (1973).

    Google Scholar 

  53. G. Vaes,On the Mechanisms of Bone Resorption. The Action of Parathyroid Hormone on the Excretion and Synthesis of Lysosomal Enzymes and on the Extracellular Release of Acid by Bone Cells, J. Cell Biol.39, 676–697 (1968).

    Google Scholar 

  54. E.L. Becker andP.M. Henson,In Vitro Studies of Immunologically Induced Secretion of Mediators from Cells and Related Phenomena, Adv. Immunol.17, 93–193 (1973).

    Google Scholar 

  55. G. Weissmann, P. Dukor andR.B. Zurier,Effect of Cyclic AMP on Release of Lysosomal Enzymes from Phagocytes, Nature (London)231, 131–135 (1971).

    Google Scholar 

  56. D.G. Wright andS.E. Malawista,The Mobilization and Extracellular Release of Granular Enzymes from Human Leukocytes during Phagocytosis, J. Cell Biol.58, 788–790 (1972).

    Google Scholar 

  57. P.M. Henson,Interaction of Cells with Immune Complexes: Adherence, Release of Constituents and Tissue Injury, J. exp. Med.134, 114s-135s (1971).

    Google Scholar 

  58. 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, 1535–1546 (1971).

    Google Scholar 

  59. P.M. Henson,The Immunologic Release of Constituents from Neutrophil Leukocytes. II. Mechanisms of Release During Phagocytosis, and Adherence to Nonphagocytosable Surfaces, J. Immunol.107, 1547–1557 (1971).

    Google Scholar 

  60. L.J. Ignarro,Nonphagocytic Release of Neutral Protease and β-Glucuronidase from Human Neutrophils. Regulation by Autonomic Neurohormones and Cyclic Nucleotides, Arthritis Rheumat.17, 25–36 (1974).

    Google Scholar 

  61. R.B. Zurier, S. Hoffstein andG. Weissmann,Mechanisms of Lysosomal Enzyme Release from Human Leukocytes. I. Effect of Cyclic Nucleotides and Colchicine, J. Cell Biol.58, 27–41 (1973).

    Google Scholar 

  62. R.B. Zurier, S. Hoffstein andG. Weissmann,Cytochalasin B: Effect on Lysosomal Enzyme Release from Human Leukocytes, Proc. Nat. Acad. Sci. U.S.A.70, 844–848 (1973).

    Google Scholar 

  63. J.L. Skosey, D. Chow, E. Damgaard andL.B. Sorensen,Effect of Cytochalasin B on Response of Human Polymorphonuclear Leukocytes to Zymosan, J. Cell Biol.57, 237–240 (1973).

    Google Scholar 

  64. G. Weissmann, R.B. Zurier andS. Hoffstein,Leukocytes as Secretory Organs of Inflammation, Agents and Actions3 (5), 370–379 (1973).

    Google Scholar 

  65. G. Weissmann, I. Goldstein, S. Hoffstein, G. Chauvet andR. Robineaux,Yin/Yang Modulation of Lysosomal Enzyme Release from Polymorphonuclear Leukocytes by Cyclic Nucleotides, Ann. N.Y. Acad. Sci.256, 222–232 (1975).

    Google Scholar 

  66. S. Hoffstein, R. Sobermann, I. Goldstein andG. Weissmann,Concanavalin A Induces Microtubule Assembly and Specific Granule Discharge in Human Polymorphonuclear Leukocytes, J. Cell Biol.68, 781–787 (1976).

    Google Scholar 

  67. I. Goldstein, J.K. Horn, H.B. Kaplan andG. Weissmann,Calcium-Induced Lysozyme Secretion from Human Polymorphonuclear Leukocytes, Biochem. Biophys. Res. Commun.60, 807–812 (1974).

    Google Scholar 

  68. F. Rossi, D. Romeo, andP. Patriarca,Metabolic Perturbation of the Inflammatory Cells, Agents and Actions6, 50–59 (1976).

    Google Scholar 

  69. A.L. Oronsky, R.J. Perper andH.C. Schroder,Phagocytic Release and Activation of Human Leukocyte Procollagenase, Nature246, 417–419 (1973).

    Google Scholar 

  70. M.S. Leffell andJ.K. Spitznagel,Intracellular and Extracellular Degranulation of Human Polymorphonuclear Azurophil and Specific Granules Induced by Immune Complexes, Infect. Immunity10, 1241–1249 (1974).

    Google Scholar 

  71. P. Brederoo andW.Th. Daems,Submicroscopic Cytology of Guinea Pig Peritoneal Exudates. I. The Heterogeneity of the Granules of Neutrophilic Granules, in:Microscopie Electronique (Ed. P. Favard; Societé Française de Microscopie Electronique, Paris, 1970), pp. 541.

    Google Scholar 

  72. D.F. Bainton,Sequential Degranulation of the Two Types of Polymorphonuclear Leukocyte Granules During Phagocytosis of Microorganisms, J. Cell Biol.58, 249–264 (1973).

    Google Scholar 

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  1. a Sandoz Research Unit, Wander Ltd., The Research Institute Wander, P.O. Box 2747, Berne, Switzerland

    Marco Baggiolini, Ursula Bretz, Beatrice Dewald & Martin E. Feigenson

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  1. Marco Baggiolini
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  2. Ursula Bretz
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  3. Beatrice Dewald
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  4. Martin E. Feigenson
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Baggiolini, M., Bretz, U., Dewald, B. et al. The polymorphonuclear leukocyte. Agents and Actions 8, 3–10 (1978). https://doi.org/10.1007/BF01972395

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