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Pathophysiology of Inflammation

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Advances in Nephrourology

Part of the book series: Ettore Majorana International Science Series ((PHYSC,volume 9))

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Abstract

Inflammation is a “surface” phenomenon triggered by immunological and non-immunological stimuli, capable of activating both humoral and cellular systems, normally present in the body in an inactive state and regulated by systemic inhibitors. Among the cellular systems, we concentrated on the mechanisms responsible for the activation of polymorphonuclear neutrophils (PMN), basophils, platelets and mononuclear phagocytes in inflammation.

As an early event in immune complex (IC)-induced inflammation, PMN aggregation and increased adhesiveness to vessel-lining endothelium appears crucial to their recruitment and sequestration at the inflammatory site. The process of PMN aggregation is triggered by several membrane-active mediators such as C5a anaphylotoxin, neutrophil-derived cationic proteins (CP) and particularly their serum carboxypeptidase-derived, desarginated products as well as a phospholipid mediator (1-O-alkyl-2-acetyl- glyceryl-3-phosphorylcholine), released from stimulated PMN, undistinguishable both structurally and functionally from the platelet-activating factor (PAF). The latter mediator may be suggested as the final common. mediator of IC-induced PMN aggregation. PMN response to chemotactic stimuli results in their emigration out of the vessels in the inflammed tissues. PMN membrane activated by specific receptors for Fc and C3b signals the initiation of metabolic and functional activities, finally leading to the discharge of their inflammatory constituents (oxygen-derived radicals, products from arachidonic acid and a series of enzymes).

Basophils are responsive in vitro to various stimuli occuring in vivo in inflammation. Besides the IgE-mediated mechanism, C3a and C5a anaphylotoxins as well as neutrophil CP have been shown to have degranulating properties on basophil-rich mixed leukocyte populations. Besides the preformed mediators such as histamine, serotonin and heparin, other substances, such as the slow-reacting substances of anaphylaxis (SRS-A) and arachidonic acid-derived metabolites, are generated as the secretory process start. As for the latter substances, PAF is released from mixed leukocyte populations challenged with C5a, CP and specific antigen concomitantly with basophil degranulation and histamine liberation.

Platelets are instrumental both in the onset and the amplification of vascular permeability during IC diseases. Their involvement may be looked at as the final end-result of many interrelating mechanism of inflammatory injury. Platelets interact with IC either directly through membrane receptors for Fc or indirectly with PAF released from IC-stimulated leukocytes as well as with injured endothelium, thus leading to platelet aggregation and “release reaction”.

Several stimuli transform circulating monocytes into their activated counterpart, the macrophages. The mechanisms responsible for the recruitment and sequestration of macrophages appear to be much like those described earlier for PMN. Macrophages infiltrate the inflammed tissues and greatly contribute as they discharge lysosomal enzymes to tissue injury. Furthermore, the recent demonstration by our laboratory that stimulated macrophages release PAF and, more interestingly, represent the richest leukocyte reservoir of this mediator, suggests that these cells also may involve platelets in inflammation.

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Abbreviations

IC:

immune complexes

PMN:

polymorphonuclear leukocytes

AA:

arachidonic acid

CP:

cationic proteins

cFMP:

3′-,5′-cyclic guanosine monophosphate

cAMP:

3′-,5′-cyclic adenosine monophosphate

HETE:

hydroxy 5′-8′-11′-14′-eicosatetranoic acid

SRS-A:

slow reacting substances of anaphylaxis

ECF-A:

eosinophil chemotactic factor of anaphylaxis

PG:

prostaglandin

PAF:

platelet-activating factor

SLE:

Systemic Lupus Erythematosus

APSGN:

Acute Post-Streptococcal Glomerulonephritis

DNA:

deoxyribonucleic acid

References

  1. Henson, P.M., Hollister, J.R., Musson, R.A., Spears, P., Henson, J.E. and Mc Carthy, K.M.: Inflammation as a surface phenomenon: Initiation of inflammatory processes by surface bound immunologic components. Adv. in Inflammation Res. (Ed. Weissmann et al.), 341. Raven Press, New York, (1979).

    Google Scholar 

  2. Müller-Eberhard, H.Y.: Complement. A. Rev. Biochem. 38: 389–413, (1969).

    Article  Google Scholar 

  3. Cochrane, C.G., Wiggins, R.C., Rewak, S.D. and Griffin, Y.H.: The Hageman factor system in inflammation. Adv. in Inflammation Res. (Ed. Weissmann et al.) 341. Ravern Press, New York, (1979).

    Google Scholar 

  4. Born, G.V.R. and Planker, M.: Toward the mechanism of the intravascular adhesion of granulocytes in inflamed vessels. Adv. in Inflammation Res. (Ed. Weissmann et al.) 11, Raven Press, New York, (1979).

    Google Scholar 

  5. Brown, D.C.: Biological activities of Complement. In “The immune system. A course on the molecular and cellular basis of Immunity”. (Ed. Hobart et al.) 274. Blackwell, Oxford, (1975).

    Google Scholar 

  6. Camussi, G., Tetta, C., Bussolino, F., Caligaris Cappio, F., Coda, R., Masera, C. and Segoloni, G.: Mediators of immune complex induced aggregation of polymorphonuclear neutrophils. C5a anaphylotoxin, neutrophil cationic proteins and their cleavage fragments. Int. Arch. Allergy appl. Immun. 62: 1–15, (1980).

    Article  Google Scholar 

  7. Camussi, G., Coda, R., Tetta, C., Bussolino, F., Stratta, P., Segoloni, G., Coppo, R. and Vercellone, A.: Immune mechanisms of PMN involvement in inflammation. In “Renal pathophysiology” (Ed. Leaf et al.) Raven Press, New York, (1980).

    Google Scholar 

  8. Camussi, G., Tetta, C., Bussolino, F., Caligaris Cappio, F., Coda, R., Masera, C. and Segoloni, G.: Mediators of immune- complex induced aggregation of PMN. II Platelet-activating factor (PAF) as the effector substance of immune-induced aggregation. Int. Arch. Allergy appl. Immun, (submitted for publ.), (1980).

    Google Scholar 

  9. Camussi, G., Bussolino, F., Tetta, C., Caligaris, F., Benveniste, J., Emanuelli, G. and Vercellone, A.: Platelet-activating factor (PAF): A mediator of immune dependent vasopermeabilization. Min. Nefr. 1: 15–18, (1980).

    Google Scholar 

  10. Henson, P.M.: The adherence of leucocytes and platelets induced by fixed IgG antibody or complement. Immunology 16: 107–121, (1969).

    Google Scholar 

  11. Lay, W.H. and Nussenrweig, V.: Receptors for complement on leucocytes. J. Exp. Med. 128: 991–1007, (1968).

    Article  Google Scholar 

  12. Weissmann, G. and Dukor, P.: The role of lysosomes in immune response. Adv. Immunol. 12: 283–295, (1970).

    Article  Google Scholar 

  13. Camussi, G., Segoloni, G., Stratta, P., Mencia-Huerta, J.M., Ragni, R., Piccoli, G. and Vercellone, A.: In vivo fixation of immune complexes on polymorphonuclear neutrophils and release of neutrophil cationic proteins in systemic lupus erythematosus. EDTA Proc., Pitman Medical (Ed. Robinson B.H.), 14: 478–482, (1977).

    Google Scholar 

  14. Camussi, G., Mencia-Huerta, J.M. and Benveniste, J.: Release of Platelet-activating factor and histamine. I. Effect of immune complex, complement and neutrophils on human and rabbit mastocytes and basophils. Immunology 33: 523–533, (1977).

    Google Scholar 

  15. Craddock, P.R., Hammerschmidt, D., Whyte, J.G., Dalmasso, A.P. and Jacob, H.: Complement (C5a)-induced granulocytes aggregation in vitro. J. Clin. Invest. 60: 260–264, (1977).

    Article  Google Scholar 

  16. Bokisch, V.A. and Müller-Eberhard, H.J.: Anaphylotoxin inac- tivator of human plasma: its isolation and characterization as a carboxypeptidase. J. Clin. Invest. 49: 2427–2436, (1970).

    Article  Google Scholar 

  17. Mc Carthy, K. and Henson, P.M.: Induction of lysosomal enzyme secretion by alveolar macrophages in response to purified complement fragments C5a and C5a des Arg. J. Immunol. 123: 2511–2517, (1979).

    Google Scholar 

  18. Benveniste, J., Henson, P.M. and Cochrane, C.G.: Leucocyte- dependent histamine release from rabbit platelets. The role of IgE, Basophils and Platelet-activating factor. J. Exp. Med. 136: 1356–1377, (1972).

    Article  Google Scholar 

  19. Pinckard, R.N., Farr, R.S. and Hanahan, D.: Physiochemical and fuctional identity of rabbit platelet-activating factor (PAF) released in vivo during IgE anaphylaxis with PAF released in vitro from IgE-sensitized basophils. J. Immunol. 123: 1847–1857, (1979).

    Google Scholar 

  20. Benveniste, J., Tence, M., Bidault, J., Boullet, C. and Polonsky, J.: Semi-synthese et structure proposée du facteur activant les plaquettes (PAF): PAF-acether, un alkyl ether analogue de la lyso-phosphatidylcholine. C.R. Acad. Sci. Paris D 289: 1037–1040, (1979).

    Google Scholar 

  21. Camussi, G., Bussolino, F., Tetta, C., Benveniste, J. and Vercellone, A.: Platelet-activating factor and glomerulonephritis. In “Endothelium, platelets and prostaglandins: fresh insight into renal diseases.” Raven Press, New York, (1980), (in press).

    Google Scholar 

  22. Camussi, G., Aglietta, M., Coda, R., Bussolino, F., Piacibello, W, and Tetta, C.: The cellular origins of human Platelet- activating factor. Immunology, (submitted for publ.) (1980).

    Google Scholar 

  23. Cazenave, J.P., Benveniste, J. and Mustard, J.F.: Aggregation of rabbit platelets by Platelet-activating factor is independent of the release reaction and the arachidonate pathway and inhibited by membrane-active drugs. Lab. Invest. 41: 275–285, (1979).

    Google Scholar 

  24. Seeman, P.: The membrane action of anesthetics and tranquillizers» Pharmacol. Rev. 24: 583–594, (1972).

    Google Scholar 

  25. Higgs, G.A., Bunting, S., Moncada, S. and Vane, J.R.: Polymorphonuclear neutrophils produce TXA2-like activity during phagocytosis. Prostaglandins. 12: 749–757, (1975).

    Google Scholar 

  26. Stossel, T.P.: Phagocytosis, recognition and ingestion. Sem. Haematol. 12: 1–28, (1975).

    Google Scholar 

  27. Scribner, D. and Fahrney, D.: Neutrophil receptors for IgG and complement. J. Immunol. 116: 892–917, (1976).

    Google Scholar 

  28. Ehlessberg, A.G. and Nussenzweig, V.: The role of membrane receptors for C3b and C3d in phagocytosis. J. Exp. Med. 145: 357–371, (1977).

    Article  Google Scholar 

  29. Weissmann, G., Korchak, H.M., Perez, D., Smolen, J.E. and Hoffstein, S.T.: Leucocytes as secretory organs in inflammation. Adv. in Inflammation Res. (Ed. Weissmann G. et al) 95. Raven Press, New York, (1979).

    Google Scholar 

  30. Ishizaka, K., Tomioka, H. and Ishizaka, T.: Mechanisms of passive sensitization. Presence of IgE and IgG molecules on human leucocytes. J. Immunol. 105: 1458–1466, (1970).

    Google Scholar 

  31. Hook, W.A., Siraganian, R.P. and Wahl, S.M.: Complement-induced histamine release from human basophils. J. Immunol. 114: 1185–1191, (1975).

    Google Scholar 

  32. Halper, J. and Metzger, H.: The interaction of IgE with rat basophilic leukemia cells. Immunochemistry 13: 907–910, (1976).

    Article  Google Scholar 

  33. Ishizaka, T., Sterk, A.R. and Ishizaka, K.: Demonstration of Fc receptors on human basophil granulocytes. J. Immunol. 123: 578–593, (1979).

    Google Scholar 

  34. Bussolino, F. and Benveniste, J.: Pharmacologic modulation of platelet-activating factor release from rabbit leucocytes. Role of cAMP. Immunology (in press), (1980).

    Google Scholar 

  35. Lichtenstein, L.M.: The mechanism of basophil histamine release induced by antigen and by calcium ionophor.e A23187. J. Immunol. 114: 1692–1699, (1975).

    Google Scholar 

  36. Sullivan, T.J. and Parker, C.W.: Pharmacologic modulation of inflammatory mediator release by mast cells. Am. J. Pathol. 85: 437–468, (1976).

    Google Scholar 

  37. Becker, E.L. and Henson, P.M.: In vitro studies of immunologically induced secretion of mediators from cells and related phenomena. Adv. Immunol. 17: 93–106, (1973).

    Article  Google Scholar 

  38. Ho, P.G. and Orange, R.P.: Indirect evidence of phospholipase A activation in purified mast cells during reserve anaphylactic challenge. Fed. Proc. 37: 1667, (1979).

    Google Scholar 

  39. Sullivan, T.J. and Parker, C.W.: Possible role of arachidonic acid and its metabolites in mediator release from rat mast cells. J. Immunol. 122: 431–440, (1979).

    Google Scholar 

  40. Roberts, L.J., Lewis, R.A., Austen, K.F. and Oades, J.A.: Arachidonic acid metabolism by rat mast cells. Prostaglandins 15: 717–720, (1978).

    Article  Google Scholar 

  41. Benveniste, J., Camussi, G. and Polonsky, J.: Platelet-activa-ting factor; Monogr. Allergy 12: 138–144, (1977).

    Google Scholar 

  42. Bussolino, F., Camussi, G. and Tetta, C.: Aggregation of human platelets by platelet-activating factor (Submitted to Agents and Actions), (1980).

    Google Scholar 

  43. Nachman, R.L. and Polley, M.: The platelet as an inflammatory cell. Adv. in inflammation Res. (Ed. Weissman G. et al), 169. Raven Press, New York, (1979).

    Google Scholar 

  44. Henson, P.M. and Cochrane, C.G.: Immune complex disease in rabbit. The role of complement and of a leucocyte-dependent release of vasoactive amines from platelets. J. Exp. Med. 133: 554–571, (1971).

    Article  Google Scholar 

  45. Müller-Eckardt, L.H. and Luscher, E.F.: Immune reactions of human blood platelets. A comparative study on the effects on platelets of heterologous anti-platelet antiserum, antigen- antibody complexes, aggregated gamma globulins and thrombin. Thrombos. Diathes. Haemorrh. 20: 821–826, (1968).

    Google Scholar 

  46. Müller-Eckardt, L.H. and Luscher, E.F.: Immune reactions of human blood platelets. The effect of latex particles with gamma globulin in relation to complement activation. Thrombos. Diathes. Haemorrh. 20: 168–176, (1968).

    Google Scholar 

  47. Camussi, G., Tetta, C., Segoloni, G. and Vercellone, A.: Immunological mechanisms of human platelet involvement. La Ricerca Clin. Lab. 8: 262–272, (1978).

    Google Scholar 

  48. Chignard, M., Le couedic, J.P., Tence, M., Vargaftig, B.B. and Benveniste, J.: The role of Platelet-activating factor in platelet aggregation. Nature 279: 799–800, (1979).

    Article  ADS  Google Scholar 

  49. Spector, W.G.: The macrophage and its derivatives. Adv. in Inflammation Res. (Ed. Weissmann G. et al.) 113. Raven Press, New York, (1979).

    Google Scholar 

  50. Cochrane, C.G.: Immunologic tissue injury mediated by neutrophilic leucocytes. Adv. Immunol. 9: 97–161, (1968).

    Article  Google Scholar 

  51. Henson, P.M.: Interaction of cells with immune complex: aherence, release of constituents and tissue injury. J. Exp. Med. 134: 1145–1335, (1971).

    Google Scholar 

  52. Kniker, W.T. and Cochrane, C.G.: Pathogenetic factors in vascular lesion of experimental serum sickness. J. Exp. Med. 127: 119–129, (1968).

    Article  Google Scholar 

  53. Camussi, G., Tetta, C. and Caligaris Cappio, F.: Detection of immune complexes on the surface of polymorphonuclear neutrophils. Int. Arch. Allergy appl, Immun. 58: 135–139, (1979).

    Article  Google Scholar 

  54. Camussi, G., Caligaris Cappio, F., Messina, M., Coppo, R., Stratta, P. and Vercellone, A.: The polymorphonuclear neutrophil (PMN) immunohistological technique: detection and characterization of the immune complexes bound to the PMN membrane in acute poststreptococcal and lupus nephritis. Clinical Nephrology (in press).

    Google Scholar 

  55. Caligaris Cappio, F., Camussi, G. and G’avosto, F.: Idiopathic neutropenia with normocellular bone marrow: an immune complex disease. British J. of Haematology 43: 595–605, (1979).

    Article  Google Scholar 

  56. Cotram, R.S.: Monocyte proliferation and glomerulonephritis. J. Lab. Clin. Med, 92: 837–840, (1978).

    Google Scholar 

  57. Screiver, G.F., Cotram, R.S., Pardo, V. and Unanue, E.R.: A mononuclear cell component in experimental immunological glomerulonephritis. J. Exp, Med. 147: 369–384, (1978).

    Article  Google Scholar 

  58. Hunsicker, L.G., Plattner, S.B. and Weisenburger, D,: The role of monocytes in serum sickness nephritis. J. Exp. Med. 150: 413–425, (1979).

    Article  Google Scholar 

  59. Monga, G., Mazzucco, G., Barbiano di Belgiojoso, G. and Busnack, C.: The presence and possible role of monocyte infiltration in human chronic proliferative glomerulonephritis. Light microscopy immunofluorescence and histochemical correlation. Am. J. Pathol. 94: 271–276, (1979).

    Google Scholar 

  60. Leibovich, S.J. and Ross, R.: A macrophage-dependent factor that stimulates the proliferation of fibroblasts in vitro. Am. J. Pathol. 84: 501–506, (1976).

    Google Scholar 

  61. Polverini, P.G., Cotran, R.S., Gimbrone, M.A. and Unanue, E.R.: Activated macrophages induce vascular proliferation. Nature 269: 804–805, (1977).

    Article  ADS  Google Scholar 

  62. Ross, R. and Vogel, A.: The platelet-derived growth factor. Cell 14: 203–207, (1978).

    Article  Google Scholar 

  63. Camussi, G., Mencia-Huerta, J.M., Segoloni, G. and Benveniste, J.: Platelet-Activating-Factor release during serum sickness. Abs. VII Congress of Nephrology, G2, (1978).

    Google Scholar 

  64. Camussi, G., Bosio, D., Segoloni, G., Tetta, C. and Vercellone, A.: Evidence for the involvement of the IgE-basophil-mastocyte system in human acute post-streptococcal glomerulonephritis. La Ricerca Clin. Lab. 8: 56–54, (1978).

    Google Scholar 

  65. Camussi, G., Benveniste, J., Tetta, C. and Vercellone, A.: Immediate hypersensitivity in Systemic Lupus Erythematosus. Abs. Vllth Int. Congress of Nephrology. G3, (1978).

    Google Scholar 

  66. Camussi, G., Tetta, C., Coda, R. and Benveniste, J.: Releaseof Platelet-Activating-Factor in human pathology. I Evidence for the occurrence of basophil degranulation and PAF release in Systemic Lupus Erythematosus (SLE). Lab. Invest- (Submitted for publication).

    Google Scholar 

  67. Cameron, J.S.: Platelets and glomerulonephritis. Nephron 18: 253–265, (1977).

    Article  Google Scholar 

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Authors and Affiliations

  1. Laboratorio di Immunopatologia Cattedra di Nefrologia Medica, Universita di Torino, Turin, Italy

    G. Camussi, C. Tetta, F. Bussolino, C. Masera & A. Vercellone

  2. Divisione di Nefrologia e Dialisi, Ospedale Maggiore S. G. Battista, Turin, Italy

    A. Vercellone

Authors
  1. G. Camussi
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  2. C. Tetta
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  3. F. Bussolino
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  4. C. Masera
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  5. A. Vercellone
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Editor information

Editors and Affiliations

  1. University Polyclinic Hospital, Palermo, Italy

    Michele Pavone-Macaluso

  2. St. James’s University Hospital, Leeds, England

    Philip H. Smith

  3. University of Turin, Turin, Italy

    Antonio Vercellone

  4. United Hospitals, Brescia, Italy

    Rosario Maiorca

  5. University Polyclinic Hospital, Palermo, Italy

    Ugo Rotolo

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© 1981 Plenum Press, New York

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Camussi, G., Tetta, C., Bussolino, F., Masera, C., Vercellone, A. (1981). Pathophysiology of Inflammation. In: Pavone-Macaluso, M., Smith, P.H., Vercellone, A., Maiorca, R., Rotolo, U. (eds) Advances in Nephrourology. Ettore Majorana International Science Series, vol 9. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-8944-6_2

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