Pathophysiology of Inflammation

  • G. Camussi
  • C. Tetta
  • F. Bussolino
  • C. Masera
  • A. Vercellone
Part of the Ettore Majorana International Science Series book series (EMISS, volume 9)


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.


Systemic Lupus Erythematosus Lysosomal Enzyme Cationic Protein Human Basophil Phagocytic Vacuole 



immune complexes


polymorphonuclear leukocytes


arachidonic acid


cationic proteins


3′-,5′-cyclic guanosine monophosphate


3′-,5′-cyclic adenosine monophosphate


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


slow reacting substances of anaphylaxis


eosinophil chemotactic factor of anaphylaxis




platelet-activating factor


Systemic Lupus Erythematosus


Acute Post-Streptococcal Glomerulonephritis


deoxyribonucleic acid


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Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • G. Camussi
    • 1
  • C. Tetta
    • 1
  • F. Bussolino
    • 1
  • C. Masera
    • 1
  • A. Vercellone
    • 1
    • 2
  1. 1.Laboratorio di Immunopatologia Cattedra di Nefrologia MedicaUniversita di TorinoTurinItaly
  2. 2.Divisione di Nefrologia e DialisiOspedale Maggiore S. G. BattistaTurinItaly

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