title: Suppression of complement activation by recombinant Crry inhibits experimental autoimmune anterior uveitis (EAAU).
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.
authors.affiliation: Department of Ophthalmology, Jones Eye Institute, Pat and Willard Walker Eye Research Center, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, AR 72205, USA.
authors.forename: Balasubramanian
authors.initials: B
authors.lastname: Manickam
authors.forename: Purushottam
authors.initials: P
authors.lastname: Jha
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Hepburn
authors.forename: B Paul
authors.initials: BP
authors.lastname: Morgan
authors.forename: Claire L
authors.initials: CL
authors.lastname: Harris
authors.forename: Puran S
authors.initials: PS
authors.lastname: Bora
authors.forename: Nalini S
authors.initials: NS
authors.lastname: Bora
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000276:immunology* / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D003167:Complement Activation / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014606:Uveitis, Anterior / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D000954:Antigens, Surface; C513105:Cr1l protein, rat; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins