Intrarenal complement activation and production have pivotal roles in progressive renal injury in chronic nephropathies. Complement has recently been implicated as a candidate mediator of inflammatory injury in the tubulointerstitial milieu during proteinuric states. A key target of the activated complement cascade 5 the proximal tubule, a site at which abnormally filtered plasma proteins and complement factors may concur to promote injury. This study investigated whether protein overloading of human cultured proximal tubular cells (HK-2) enhanced complement activation, possibly via impairment of complement regulation. HK-2 cells exposed to albumin, transferrin or IgG followed by human serum (HS) as a complement source, showed increased apical C3 and membrane attack complex deposition compared to HS exposure alone. Complement deposition occurred through the activation of the alternative pathway. Albumin and complement challenge had additive proinflammatory effects, shown by greater increases in fractalkine and TGF-p mRNA expression compared to each stimulus alone. Factor H binds to the cell surface through heparan sulfate residues. Protein overload reduced heparan sulfate surface density, resulting in decreased factor H binding and increased active C3b deposition. Thus, protein overload alters tubular cell phenotype by reducing the cell's capability to counteract complement activation.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:497398 |
| Date | January 2008 |
| Creators | Buelli, Simona |
| Publisher | Open University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
Page generated in 0.0018 seconds