title: Heteropolymer-mediated clearance of immune complexes via erythrocyte CR1: mechanisms and applications.
abstract: Opsonization of particulate pathogens by antibodies and complement can lead to their binding to the complement receptor (CR1), specific for C3b, on primate erythrocytes (E). This process of immune adherence may play a role in immunologic defense by immobilizing bacteria and viruses, thus preventing them from leaving the bloodstream to invade susceptible tissue and organs. Immune adherence of C3b-opsonized and immune complexed pathogens to E may also facilitate their transfer to, and destruction by, fixed tissue macrophages. We have used mAbs specific for CR1 crosslinked with pathogen specific mAbs to generate heteropolymers (HP) which can bind a wide range of substrates to primate erythrocytes. Both prototype and bonafide pathogens bound to primate E via HP are handled in the circulation of non-human primates in a manner which appears to be virtually identical to the mechanism by which C3b-opsonized substrates bound to E CR1 are cleared. In this process of focused phagocytosis, Fc receptors on the phagocytic cell engage the E-bound complex, CR1 is removed by proteolysis, and the entire immune complex and CR1 are internalized while sparing the E. It may be possible to use HP to target pathogens in the bloodstream in a wide range of therapeutic applications.
authors.affiliation: Department of Biochemistry and Molecular Genetics, Universsity of Virginia Health System, Charlottesville, VA, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Lindorfer
authors.forename: C S
authors.initials: CS
authors.lastname: Hahn
authors.forename: P L
authors.initials: PL
authors.lastname: Foley
authors.forename: R P
authors.initials: RP
authors.lastname: Taylor
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001704:Biopolymers / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology*; D006801:Humans; D007104:Immune Adherence Reaction; D018448:Models, Immunological; D017463:Receptors, Complement 3b / Q000276:immunology*
chemical_list: D000936:Antigen-Antibody Complex; D001704:Biopolymers; D017463:Receptors, Complement 3b