Lung eosinophilic inflammation and airway hyperreactivity are enhanced by murine anaphylactic, but not nonanaphylactic, IgG1 antibodies.
BACKGROUND
Chronic airway inflammation is a fundamental feature of bronchial asthma, which is characterized by the accumulation and activation of inflammatory cells, such as mast cells and eosinophils, that are tightly regulated by TH2 cytokines and chemokines. Recently, we demonstrated, in a murine model of asthma with immunosuppressed mice reconstituted with antigen-specific IgE or IgG1 antibodies, that IgE, but not IgG1, participates in potentiation of airway inflammation and induction of airway hyperreactivity (AHR). The IgG1 antibody, however, did not elicit passive cutaneous anaphylactic reactions, which was in contrast to IgE.


OBJECTIVE
Because 2 types of murine IgG1 have been demonstrated with regard to anaphylactic activity, the present experiments were undertaken to determine the role of anaphylactic and nonanaphylactic IgG1 antibodies in the development of antigen-induced eosinophilia and AHR in this model.


METHODS
Dinitrophenyl-conjugated, heat-coagulated hen's egg white was implanted in immunosuppressed mice reconstituted with anaphylactic or nonanaphylactic IgG1. Intratracheal challenge with aggregated dinitrophenyl-ovalbumin was performed on day 14, and lung inflammatory and mechanical parameters were evaluated after 48 hours.


RESULTS
Our results demonstrated that reconstitution of immunosuppressed mice with anaphylactic IgG1 antibodies in contrast to nonanaphylactic IgG1 antibodies potentiates their ability to have pulmonary eosinophilic inflammation and AHR. IL-5 and eotaxin levels in bronchoalveolar lavage fluid from anaphylactic IgG1-reconstituted mice were also higher than those in nonanaphylactic IgG1-reconstituted mice.


CONCLUSIONS
These results indicate that the anaphylactic property of murine IgG1 molecules is essential for their capacity to enhance lung eosinophilic inflammation and to induce AHR.
Macedo-Soares
Maria Fernanda
MF
Laboratory of Immunopathology, Butantan Institute, São Paulo, Brazil. mamacedo@usp.br
Itami
Denise M
DM
Lima
Carla
C
Perini
Adenir
A
Faquim-Mauro
Eliana L
EL
Martins
Milton A
MA
Macedo
Mahasti S
MS
D000707:Anaphylaxis / Q000276:immunology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000032:analysis; D002631:Chemotactic Factors, Eosinophil / Q000032:analysis; D004802:Eosinophilia / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D015848:Interleukin-5 / Q000032:analysis; D008168:Lung / Q000276:immunology; D008171:Lung Diseases / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal
C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D007074:Immunoglobulin G; D015848:Interleukin-5