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 th e 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 rhesu s monkeys and human beings were passively sensitized for 20 hours with serum from a ragweed-sensitive patient in tile presence of 0, 1-, 5-, or 10-fold concentrations of the inhibitors relative to IgE. The pare nchymal strips were then suspended in a superfusion apparatus for meas urement of isometric tone and collection of superfusate for histamine analysis in response to challenge with antigen E (AgE). Nonsensitized tissues did nor react to AgE challenge whereas AgE challenge of passiv ely sensitized tissues resulted in a time-dependent parenchymal contra ction and histamine release. Both FcERT-IgC and MaE11 completely aboli shed the AgE-induced contraction and histamine release in a dose-depen dent manner. rn addition, passively sensitized lung tissues failed to respond to direct challenge with either FcERT-IgG or MaE11. The result s of this study suggest that FcERI-IgG and MaE11 may have important im munotherapeutic benefit for the amelioration of IgE-mediated diseases.