Immunologic assessment of host defense impairment in patients with septic multiple organ failure: relationship between complement activation and changes in neutrophil function

Surgery. 1994 Feb;115(2):145-55.

Abstract

Background: The pathogenesis of gram-negative sepsis-induced multiple organ failure (MOF) remains to be elucidated.

Methods: Blood samples were obtained from eleven patients with septic MOF, three patients with sepsis, three patients who underwent operation, and three healthy volunteers. In these patients the relationship between changes in polymorphonuclear neutrophil (PMN) function and complement activation was investigated.

Results: PMNs from patients with sepsis exhibited enhanced endothelial cell adhesion, enhanced chemotaxis, increased oxygen radical generation, and increased lysosomal enzyme release. Although PMNs from patients with septic MOF also exhibited enhanced adhesion and chemical mediator production, chemotaxis was markedly depressed. Complement activation in septic MOF was indicated by decreases in total complement activity and complement component 4 (C4) and increases in C3a and C4a des-Arginine. Increases in plasma concentrations of circulating immunoglobulin G immune complexes and decreases in PMN Fc gamma R expression suggest that the classic pathway is the main pathway of complement activation. On the other hand, we could not detect decreases in C4 or increases in C4a des-Arginine in patients with sepsis, suggesting that the alternate pathway is the main pathway of complement activation. Increases in serum concentrations of the membrane attack (SC5b-9) complex also suggested that activated complement itself may participate in organ injury in patients with septic MOF. Moreover, PMN up-regulation of surface inhibitory factors of complement activation likely allows these neutrophils to survive and function.

Conclusions: The combination of changes in PMN function and complement activation appears to be intimately associated with the pathogenesis of septic MOF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigen-Antibody Complex / analysis
  • Cell Adhesion
  • Chemotaxis, Leukocyte
  • Complement Activation*
  • Cytotoxicity Tests, Immunologic
  • Endothelium, Vascular / cytology
  • Female
  • Gram-Negative Bacterial Infections / complications*
  • Humans
  • Immune System / physiopathology*
  • Male
  • Middle Aged
  • Multiple Organ Failure / etiology*
  • Multiple Organ Failure / immunology*
  • Neutrophils / physiology*
  • Receptors, Fc / analysis

Substances

  • Antigen-Antibody Complex
  • Receptors, Fc