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Suppression of complement activation by recombinant Crry inhibits experimental autoimmune anterior uveitis (EAAU)

Manickam, Balasubramanian, Jha, Purushottam, Hepburn, Natalie Jayne, Morgan, Bryan Paul, Harris, Claire Louise, Bora, Puran S. and Bora, Nalini S. 2010. Suppression of complement activation by recombinant Crry inhibits experimental autoimmune anterior uveitis (EAAU). Molecular Immunology 48 (1-3) , pp. 231-239. 10.1016/j.molimm.2010.08.006

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Abstract

This study was initiated to explore the effect of recombinant rat Crry linked to the Fc portion of rat IgG2a (Crry-Ig) on the induction of experimental autoimmune anterior uveitis (EAAU) and on established disease. EAAU was induced in Lewis rats by immunization with bovine melanin-associated antigen (MAA). MAA sensitized animals received Crry-Ig, rat IgG2a (isotype control) or PBS separately before the onset of EAAU or after the onset of clinical disease. Administration of Crry-Ig suppressed the induction of EAAU while all animals injected with IgG2a or PBS developed the normal course of EAAU. Treatment with Crry-Ig resulted in the suppression of ocular complement activation as well as the functional activity of complement in the peripheral blood. At the peak of EAAU, levels of IFN-γ, IP-10, ICAM-1 and LECAM-1 were significantly reduced within the eyes of Crry-Ig treated Lewis rats. Importantly, administration of Crry-Ig even after the onset of EAAU resulted in a sharp decline in the disease activity and early resolution of EAAU. Collectively, the evidence presented here demonstrate that inhibition of complement by Crry-Ig results in low levels of inflammatory molecules-C3 activation products, MAC, cytokines, chemokines and adhesion molecules in the eye. Down-regulation of these molecules affects the infiltration and recruitment of inflammatory cells to the eye resulting in the inhibition of EAAU.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Ocular autoimmunity; Complement system; C3; Crry (complement-related gene/protein y, 512 antigen); Membrane attack complex (MAC); Uveitis
Publisher: National Institute of Health
ISSN: 0161-5890
Last Modified: 20 Oct 2017 17:50
URI: http://orca.cf.ac.uk/id/eprint/18965

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