Immunoglobulin E antibodies enhance pulmonary inflammation induced by inhalation of a chemical hapten.
BACKGROUND
Occupational exposure to chemicals is an important cause of asthma. Recent studies indicate that IgE antibodies enhance sensitization to chemicals in the skin.


OBJECTIVE
We investigated whether IgE might similarly promote the development of airway inflammation following inhalation of a contact sensitizer.


METHODS
A model of chemical-induced asthma is described in which introduction of the low-molecular-weight compound, trinitrobenzene sulphonic acid (TNBS), via the respiratory tract was used for both sensitization and challenge. The role of IgE antibodies in the immune response to inhaled TNBS in this model was assessed by comparing the responses of wild-type (WT) and IgE-deficient (IgE(-/-)) mice on the BALB/c background. Reconstitution of circulating IgE levels by intravenous injection of IgE antibodies into IgE(-/-) mice before sensitization was performed to confirm the role of IgE in any differences observed between the responses of WT and IgE(-/-) mice.


RESULTS
Intranasal challenge of TNBS-sensitized (but not sham-sensitized control mice) induced intense pulmonary inflammation. Macrophages, eosinophils and lymphocytes, including T, B, natural killer and natural killer T cells, were recruited to the airway and the animals displayed bronchial hyperresponsiveness (BHR) to methacholine. Serum levels of murine mast cell protease-1 (mMCP-1) were elevated suggesting mast cell activation. In contrast, the development of airway inflammation, recruitment of lymphocytes, induction of BHR and production of mMCP-1 were all significantly attenuated in IgE-deficient mice. Reconstitution of IgE(-/-) mice with IgE (of unrelated antigen specificity) before sensitization partially restored these features of asthma.


CONCLUSIONS
Our data indicate that IgE antibodies non-specifically enhance the development of airway inflammation induced by exposure to chemical antigens.
Mathias
C B
CB
Division of Immunology, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA.
Freyschmidt
E-J
EJ
Oettgen
H C
HC
D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D018932:Chemokine CCL2 / Q000097:blood; D004136:Dinitrobenzenes / Q000276:immunology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000166:cytology; D006241:Haptens / Q000276:immunology*; D007114:Immunization / Q000379:methods; D007073:Immunoglobulin E / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D007694:Killer Cells, Natural / Q000166:cytology; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008679:Metaplasia / Q000473:pathology; D016210:Methacholine Chloride; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000166:cytology; D009784:Occupational Diseases / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology; D014302:Trinitrobenzenesulfonic Acid / Q000276:immunology
C509872:2,4-dinitrobenzene; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004136:Dinitrobenzenes; D006241:Haptens; D016210:Methacholine Chloride; D007073:Immunoglobulin E; D014302:Trinitrobenzenesulfonic Acid