Human FcERI-IgG and humanized anti-IgE monoclonal antibody MaE11 block passive sensitization of human and rhesus monkey lung.
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.
Saban
R
R
Department of Surgical Sciences, School of Veterinary Medicine University of Wisconsin, Madison 53706.
Haak-Frendscho
M
M
Zine
M
M
Ridgway
J
J
Gorman
C
C
Presta
L G
LG
Bjorling
D
D
Saban
M
M
Jardieu
P
P
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*
D000911:Antibodies, Monoclonal; D000941:Antigens; D007074:Immunoglobulin G; D017455:Receptors, IgE; D007073:Immunoglobulin E