May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Investigation of the Interactions Between Complement Factor H, C3b, and Amyloid β
Author Affiliations & Notes
  • U. L. Kelly
    Duke University Eye Center, Durham, North Carolina
    Ophthalmology,
  • E. Mina
    Pfizer Inc., Rinat Laboratories, California
  • J. Lin
    Pfizer Inc., Rinat Laboratories, California
  • J. Ding
    Duke University Eye Center, Durham, North Carolina
    Ophthalmology,
  • G. Hageman
    Ophthalmology, University of Iowa, Hospital and Clinics, Iowa
  • V. Arshavsky
    Duke University Eye Center, Durham, North Carolina
    Ophthalmology,
  • H. Jiang
    Pediatrics, Duke University Medical Center, Durham, North Carolina
  • M. Frank
    Pediatrics, Duke University Medical Center, Durham, North Carolina
  • C. Bowes Rickman
    Duke University Eye Center, Durham, North Carolina
    Ophthalmology and Cell Biology,
  • Footnotes
    Commercial Relationships  U.L. Kelly, None; E. Mina, None; J. Lin, None; J. Ding, None; G. Hageman, None; V. Arshavsky, None; H. Jiang, None; M. Frank, None; C. Bowes Rickman, None.
  • Footnotes
    Support  FFB individual grant, Steinbach Fund, RPB core
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5155. doi:https://doi.org/
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      U. L. Kelly, E. Mina, J. Lin, J. Ding, G. Hageman, V. Arshavsky, H. Jiang, M. Frank, C. Bowes Rickman; Investigation of the Interactions Between Complement Factor H, C3b, and Amyloid β. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5155. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Amyloid β (Aβ), complement component C3b and complement factor H have been identified in drusen. We studied the effects of Aβ1-40 and 1-42, in different aggregation states, on the cofactor activity of purified, allotypic variant-specific isoforms of factor H in the factor I - mediated proteolytic cleavage of C3b. We then determined whether this modulation was due to direct C3b-Aβ interaction or to factor H-Aβ binding.

Methods: : Factor H was purified from plasma from individuals homozygous for the double variants: I44/Y384 (aka I62/Y402), V44/Y384 and V44/H384. Fluid-phase and cell-based assays of the cofactor activity of factor H were used to establish the effect on the kinetics of the reaction when Aβ, in various aggregation states, was introduced to the assay. The binding of Aβ on a solid surface to variant-specific factor H was investigated. The direct effect of Aβ on C3b was evaluated using silver-stained gels and Westerns, and aggregation was visualized using C3b-coated sheep erythrocytes. The ability of factor H to influence this reaction was also investigated.

Results: : Monomeric Aβ1-40 increased the rate of proteolytic cleavage of C3b by factor I and factor H in both the fluid-phase and cell-based assays. This modulation was not variant specific. Oligomeric Aβ1-42 decreases the rate of this reaction. Purified, variant-specific factor H was added to Aβ of different lengths and aggregation states (mono-, oligomeric or fibrillar) on a plastic plate. Oligomeric Aβ1-42 exhibited the highest binding overall with all three forms of factor H. Oligomeric and, to a lesser extent, fibrillar Aβ 1-42 aggregate C3b at certain concentrations and this aggregation could be partially inhibited by the presence of factor H.

Keywords: age-related macular degeneration • inflammation • drusen 
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