R. Saban et al., HUMAN FCERI-IGG AND HUMANIZED ANTI-IGE MONOCLONAL-ANTIBODY MAE11 BLOCK PASSIVE SENSITIZATION OF HUMAN AND RHESUS-MONKEY LUNG, Journal of allergy and clinical immunology, 94(5), 1994, pp. 836-843
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.