Inhibition of the alternative pathway of complement activation reduces inflammation in experimental autoimmune uveoretinitis

Mei Chen, Elizabeth Muckersie, Chang Luo, John V Forrester, Heping Xu

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

We have shown previously that complement factor H (CFH) and complement factor B (CFB) are constitutively expressed by retinal pigment epithelial cells and their production is regulated by inflammatory cytokines, suggesting that the alternative pathway (AP) of complement activation might play a role in retinal inflammation. In this study, we further investigated the role of the AP in retinal inflammation using experimental autoimmune uveoretinitis (EAU) as a model. Mice with EAU show increased levels of C3d deposition and CFB expression in the retina. Retinal inflammation was suppressed clinically and histologically by blocking AP-mediated complement activation with a complement receptor of the Ig superfamily fusion protein (CRIg-Fc). In line with reduced inflammation, C3d deposition and CFB expression were markedly decreased by CRIg-Fc treatment. Treatment with CRIg-Fc also led to reduced T-cell proliferation and IFN-¿, TNF-a, IL-17, and IL-6 cytokine production by T cells, and reduced nitric oxide production in BM-derived macrophages. Our results suggest that AP-mediated complement activation contributes significantly to retinal inflammation in EAU. CRIg-Fc suppressed retinal inflammation in EAU by blocking AP-mediated complement activation with probable direct effects on C3/C5 activation of macrophages, thus leading to reduced nitric oxide production by infiltrating CRIg(-) macrophages.
Original languageEnglish
Pages (from-to)2870-2881
Number of pages12
JournalEuropean Journal of Immunology
Volume40
Issue number10
Early online date30 Aug 2010
DOIs
Publication statusPublished - Oct 2010

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Alternative Complement Pathway
Inflammation
Complement Factor B
Nitric Oxide
Macrophages
Cytokines
T-Lymphocytes
Complement Factor H
Complement Receptors
Retinal Pigments
Macrophage Activation
Interleukin-17
Retina
Interleukin-6
Epithelial Cells
Cell Proliferation
Proteins

Keywords

  • animals
  • autoimmunity
  • complement activation
  • complement C3b
  • complement Factor B
  • complement pathway, alternative
  • cytokines
  • disease models, animal
  • female
  • immunohistochemistry
  • lymphocyte activation
  • mice
  • mice, inbred C57BL
  • nitric oxide synthase type II
  • RNA
  • receptors, complement
  • retinitis
  • reverse transcriptase polymerase chain reaction
  • T-lymphocytes

Cite this

Inhibition of the alternative pathway of complement activation reduces inflammation in experimental autoimmune uveoretinitis. / Chen, Mei; Muckersie, Elizabeth; Luo, Chang; Forrester, John V; Xu, Heping.

In: European Journal of Immunology, Vol. 40, No. 10, 10.2010, p. 2870-2881.

Research output: Contribution to journalArticle

Chen, Mei ; Muckersie, Elizabeth ; Luo, Chang ; Forrester, John V ; Xu, Heping. / Inhibition of the alternative pathway of complement activation reduces inflammation in experimental autoimmune uveoretinitis. In: European Journal of Immunology. 2010 ; Vol. 40, No. 10. pp. 2870-2881.
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