title: Human FcERI-IgG and humanized anti-IgE monoclonal antibody MaE11 block passive sensitization of human and rhesus monkey lung.
abstract: IgE antibodies are thought to play an important role in the induction of allergic inflammation of the bronchi. In this study we assessed the capacity of two inhibitors, FcERI-IgG, an immunoadhesin made up of the alpha chain of the high-affinity IgE receptor joined to a truncated IgG heavy chain, and MaE11, a humanized murine anti-human IgE antibody, to prevent allergen sensitization. Lung parenchyma strips from rhesus monkeys and human beings were passively sensitized for 20 hours with serum from a ragweed-sensitive patient in the presence of 0, 1-, 5-, or 10-fold concentrations of the inhibitors relative to IgE. The parenchymal strips were then suspended in a superfusion apparatus for measurement of isometric tone and collection of superfusate for histamine analysis in response to challenge with antigen E (AgE). Nonsensitized tissues did not react to AgE challenge, whereas AgE challenge of passively sensitized tissues resulted in a time-dependent parenchymal contraction and histamine release. Both FcERI-IgG and MaE11 completely abolished the AgE-induced contraction and histamine release in a dose-dependent manner. In addition, passively sensitized lung tissues failed to respond to direct challenge with either FcERI-IgG or MaE11. The results of this study suggest that FcERI-IgG and MaE11 may have important immunotherapeutic benefit for the amelioration of IgE-mediated diseases.
authors.affiliation: Department of Surgical Sciences, School of Veterinary Medicine University of Wisconsin, Madison 53706.
authors.forename: R
authors.initials: R
authors.lastname: Saban
authors.forename: M
authors.initials: M
authors.lastname: Haak-Frendscho
authors.forename: M
authors.initials: M
authors.lastname: Zine
authors.forename: J
authors.initials: J
authors.lastname: Ridgway
authors.forename: C
authors.initials: C
authors.lastname: Gorman
authors.forename: L G
authors.initials: LG
authors.lastname: Presta
authors.forename: D
authors.initials: D
authors.lastname: Bjorling
authors.forename: M
authors.initials: M
authors.lastname: Saban
authors.forename: P
authors.initials: P
authors.lastname: Jardieu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D000941:Antigens / Q000276:immunology; D006636:Histamine Release; D006801:Humans; D007116:Immunization, Passive; D007073:Immunoglobulin E / Q000276:immunology*; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology*; D066298:In Vitro Techniques; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D008253:Macaca mulatta; D017455:Receptors, IgE / Q000737:chemistry / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens; D007074:Immunoglobulin G; D017455:Receptors, IgE; D007073:Immunoglobulin E