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Alternative pathway complement activation induces proinflammatory activity in human proximal tubular epithelial cells
S David1, L Biancone, C Caserta
1Cattedra di Nefrologia, Facoltà di Medicina e Chirurgia, Università di Parma, Italy.
Summary
Complement activation on kidney proximal tubular cells triggers inflammation. This process releases inflammatory mediators like IL-6 and TNF-alpha, potentially contributing to tubulointerstitial injury.
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- Proximal tubular epithelial cells possess C3-convertase activity, leading to complement (C) fixation and membrane attack complex (MAC) insertion.
- The pathological impact of MAC insertion on these cells remains unclear.
Purpose of the Study:
- To investigate the consequences of complement fixation on proximal tubular epithelial cells.
- To determine the effect of complement activation on inflammatory mediator production.
Main Methods:
- Human proximal tubular epithelial cells were cultured and exposed to normal or heat-inactivated human serum.
- Calcium influx, 14C-arachidonic acid release, prostaglandin E2, IL-6, and TNF-alpha production were measured.
- Experiments utilized C6-deficient sera and Mg2+/EGTA to elucidate complement-dependent pathways.
Main Results:
- Complement fixation induced time-dependent calcium influx and 14C-arachidonic acid release, inhibited by a phospholipase A2 inhibitor.
- Complement fixation stimulated the release of prostaglandin E2, IL-6, and TNF-alpha.
- The release of these mediators was dependent on the terminal complement components, specifically C5b-9 insertion.
Conclusions:
- In vitro complement activation on proximal tubular cells generates proinflammatory mediators.
- These mediators may play a role in the development of tubulointerstitial injury.