title: Effect of carbohydrate modification on the localization of human polyclonal IgG at focal sites of bacterial infection.
abstract: Radiolabeled human polyclonal IgG localizes at focal sites of infection/inflammation. Previous studies have sought to identify the mechanism of localization, but the relative importance of specific antigen recognition by individual antibody molecules, binding to Fc receptors on inflammatory cells and nonspecific processes such as increased tissue permeability remains uncertain. This study was performed to evaluate the specific role of Fc receptor binding as a mechanism of localization. The Fc region of IgG was modified by endoglycosidase-F digestion and periodate oxidation to reduce the binding of IgG to Fc receptors. In-vitro binding was tested in an Fc receptor binding assay using the human monocyte-like cell line, U937. The in-vivo ability of the modified antibodies to localize at focal sites of E. coli infection was tested by biodistribution studied with the 111In-labeled proteins. Modification of the carbohydrate moiety of the Fc region of IgG resulted in a marked decrease in Fc receptor binding in vitro; with antibody concentrations of 1 micrograms/ml (which is presumed to exist at infected sites) showing no binding for endoglycosidase modified IgG and 50% binding for periodate modified IgG. In contrast, in-vivo infection localization as measured by level of accumulation or target-to-background ratio was not significantly effected by carbohydrate modification. These studies suggest that the contribution of Fc receptor binding to IgG localization at sites of infection is minimal.
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Boston.
authors.forename: A J
authors.initials: AJ
authors.lastname: Fischman
authors.forename: A J
authors.initials: AJ
authors.lastname: Fucello
authors.forename: J L
authors.initials: JL
authors.lastname: Pellegrino-Gensey
authors.forename: J
authors.initials: J
authors.lastname: Geltofsky
authors.forename: M L
authors.initials: ML
authors.lastname: Yarmush
authors.forename: R H
authors.initials: RH
authors.lastname: Rubin
authors.forename: H W
authors.initials: HW
authors.lastname: Strauss
mesh_terms: D000818:Animals; D002241:Carbohydrates / Q000502:physiology*; D004927:Escherichia coli Infections / Q000000981:diagnostic imaging*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D004369:Pentetic Acid; D011877:Radionuclide Imaging; D051381:Rats; D011919:Rats, Inbred Strains; D011961:Receptors, Fc / Q000378:metabolism*
chemical_list: D002241:Carbohydrates; D007074:Immunoglobulin G; D011961:Receptors, Fc; D004369:Pentetic Acid