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

Manickam, Balasubramanian, Jha, Purushottam, Hepburn, Natalie Jayne, Morgan, Bryan Paul ORCID: https://orcid.org/0000-0003-4075-7676, 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:	19 Oct 2022 08:46
URI:	https://orca.cardiff.ac.uk/id/eprint/18965

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