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Abstract: TH-PO956

Complement 3 Mediated Macrophage Polarization Contributes to Renal Interstitial Fibrosis

Session Information

Category: Pathology and Lab Medicine

  • 1501 Pathology and Lab Medicine: Basic

Author

  • Wan, Jian-xin, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
Background

To explore regulation of complement 3 (C3) on polarization of interstitial macrophages and related outcomes in renal fibrosis.

Methods

C57 BL/6 wild type and C3-deficient mice were created for UUO and sacrificed at days 3, 7, 14 after the operation. Obstructed kidneys were collected and assessed. Expression of C3 in kidneys was detected by immunohistochemical staining. Phenotypes of interstitially infiltrated macrophages, interstitial fibrosis, peritubular capillary density, expression of VEGF and inflammatory cytokines were compared between wild type and C3-deficient UUO mice. Propotion of macrophage phenotypes were identified by double immunofluorescence for F4/80 and iNOS or CD206, western blot for iNOS, Arg-1 and CD206. Paraffin sections were stained with HE and Masson’s trichrome. Score of tubulointerstitial injury and percent of renal interstitial fiobrotic area were obtained. Peritubular capillary density was detected by CD31 immunohistochemical staining. VEGF164, sVEGFR1, TNF-α, IL-10 were examined by real time quantitative PCR and western blot. Wild type and C3-deficient UUO mice were treated by liposome clodronate in early or late stage respectively then interstitially infiltrated macrophages and interstitial fibrosis were analysed.

Results

C3-deficient UUO mice had milder degree of tubulointerstitial fibrosis and fewer M1 but more M2 interstitial infiltration in early stage compared with wild type mice. This macrophage polarization shift was accompanied with decreased expression of TNF-α and sVEGFR1, increased expression of IL-10 and VEGF164 in kidney, as well as increased peritubular capillary density. Depletion of macrophages ameliorated renal fibrosis in wild type UUO mice but had no effect on C3-deficient UUO mice.

Conclusion

Complement 3 activation has a close relationship with renal interstitium infiltrating macrophages and fibrosis, and contributes to renal interstitial fibrosis by promotion of macrophage polarization, increasement of inflammatory cytokines, reduction of peritubular capillary density in kidney.