Alternative pathway complement activation induces proinflammatory activity in human proximal tubular epithelial cells

Nephrol Dial Transplant. 1997 Jan;12(1):51-6. doi: 10.1093/ndt/12.1.51.


Background: Proximal tubular epithelial cells express a surface C3-convertase activity which induces C fixation and insertion of the C5b-9 membrane attack complex (MAC) into the cell plasma membrane. The physiopathological consequences of this phenomenon are unknown.

Methods: The effect of C fixation on the production of inflammatory mediators by human proximal tubular epithelial cells in culture was explored.

Results: Proximal tubular epithelial cells incubated with a sublytic amount of normal human serum as a source of C, but not with heat-inactivated human serum, showed a time-dependent calcium influx and a concomitant release of 14C-arachidonic acid (14C-AA). Eicosanoid synthesis following the arachidonic acid mobilization was studied as prostaglandin E2 release. Mg2+/EGTA, which did not prevent C activation by the C3-convertase, and p-bromodiphenacyl bromide a phospholipase A2-inhibitor, inhibited mobilization of 14C-AA. These results suggest the activation of an extracellular Ca(2+)-dependent, phospholipase A2. Complement fixation was associated with the synthesis of proinflammatory cytokines such as IL-6 and TNF-alpha. Experiments with C6-deficient sera indicated that the release of 14C-AA and the production of cytokines were dependent on the insertion of the terminal components of complement in the plasma membrane. Indeed, the reconstitution of normal haemolytic activity of C6-deficient sera with purified C6 restored also the release of 14C-AA and the production of cytokines.

Conclusions: In vitro complement activation on the proximal tubular cell surface triggers the generation of proinflammatory mediators, which may potentially contribute to the pathogenesis of tubulointerstitial injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonic Acid / metabolism
  • Calcium / metabolism
  • Complement Pathway, Alternative / physiology*
  • Cytokines / biosynthesis
  • Epithelium / immunology
  • Epithelium / injuries
  • Epithelium / physiology
  • Glomerulonephritis / etiology
  • Glomerulonephritis / immunology
  • Glomerulonephritis / physiopathology
  • Humans
  • In Vitro Techniques
  • Inflammation Mediators / physiology*
  • Kidney Tubules, Proximal / immunology
  • Kidney Tubules, Proximal / injuries
  • Kidney Tubules, Proximal / physiology*


  • Cytokines
  • Inflammation Mediators
  • Arachidonic Acid
  • Calcium