Suppression of immediate and late responses to antigen by a non-anaphylactogenic anti-IgE antibody in a murine model of asthma.
Eosinophils are recruited to the airways during allergic reactions, but animal models have shown that their mere presence is not sufficient for the development of bronchopulmonary hyperreactivity. Other factors, such as immunoglobulin (Ig)E, seem to be required. Using mice selected for the production of large amounts of IgE, the effects of antibody neutralization of IgE on antigen-induced lung recruitment of eosinophils and induction of bronchopulmonary hyperreactivity and of other indicators of inflammation were studied. A monoclonal non-anaphylactogenic rat anti-mouse IgE (mAb1-5), given within 24 h of the challenge with antigen, reduced tissue eosinophilia, the recruitment of IgE-bearing cells identified as basophils, mucous cell metaplasia, anaphylactic bronchoconstriction and bronchopulmonary hyperreactivity. mAb1-5 inhibited interleukin (IL)4 titres in the bronchoalveolar lavage fluid, but not those of I1-5. Inhibition by mAb1-5 may result from competitive displacement of immunoglobulin E from its different receptors, thus preventing cell stimulation. Moreover, the inhibition of the massive recruitment of immunoglobulin E-bearing basophils into the lungs within hours after challenge and of interleukin4 production by mAb1-5 may be important factors leading to the reduction of pulmonary eosinophilia and bronchopulmonary hyperreactivity. Thus, immunoglobulin (Ig)E and allergic IgE-bearing cells seem to play an essential role in the initial development of the late allergic airway responses.
Unité d'Histopathologie, Institut Pasteur-INSERM, Paris, France.
S
S
Haile
J
J
Lefort
S Y
SY
Eum
C
C
Dumarey
M
M
Huerre
C
C
Heusser
B B
BB
Vargaftig
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D001491:Basophils / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000503:physiopathology; D004804:Eosinophils / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology* / Q000502:physiology; D008168:Lung / Q000276:immunology / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D013997:Time Factors
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; C026408:anti-IgE antibodies; D007073:Immunoglobulin E; D010047:Ovalbumin