BCG modulation of anaphylactic antibody response, airwayinflammation and lung hyperreactivity in geneticallyselected mouse strains (Selection IV-A)

The effect of Bacillus Calmette–Gue´rin (BCG) treatment in allergic pulmonary reaction was studied in micegenetically selected accordingly to a High (H-IVA) or Low (L-IVA) antibody responsiveness. Mice wereimmunized with ovalbumin (OVA) or OVA plus BCG. Two days after nasal antigenic challenge, seric IgE andIgG1 anti-OVA, eosinophils in pulmonary tissue, inflammatory cells in bronchoalveolar lavage and the complianceand conductance of respiratory system were evaluated. H-IVA mice were found more susceptible than L-IVA, andBCG was able to inhibit simultaneously the production of IgE, the bronchopulmonary inflammation and bronchialhyperresponsiveness in these genetically selected mice.

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. Objectives 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.

Modulation of eosinophil migration from bone marrow to lungs of allergic rats by nitric oxide

Chronic blockade of nitric oxide (NO) synthesis attenuates the eosinophil infiltration into airways of allergic rats. This study was designed to investigate whether the inhibition of eosinophil influx to the lung of allergic rats reflects modifications in the pattern of cell mobilization from the bone marrow to peripheral blood and/or to lung. Male Wistar rats were treated with Nù-nitro-L-arginine methyl ester (L-NAME; 20 mg/rat per day) for 4 weeks and sensitized with ovalbumin (OVA). In control rats, the pulmonary OVA-challenge promoted an early (24 h) increase in the bone marrow eosinophil population that normalized at 48 h after OVA-challenge, at which time the eosinophils disappeared from the blood and reached the lungs in mass. In L-NAME-treated rats, an accumulation of eosinophils in bone marrow was observed at 24 and 48 h post-OVA-challenge. No variation in this cell type number was observed in peripheral blood and bronchoalveolar lavage throughout the time-course studied. In control rats, the adhesion of bone marrow eosinophils to fibronectin-covered wells was significantly increased at 24 h after OVA-challenge, whereas in L-NAME-treated rats the increased adhesion was detected at 48 h. A 32% decrease in the expression of inducible nitric oxide synthase (iNOS) (but not endothelial nitric oxide synthase; eNOS) in eosinophils from L-NAME-treated rats was observed. The levels of IgE, IgG1 and IgG2a were not affected by the L-NAME treatment. Our findings suggest that inhibition of NO synthesis upregulates the binding of eosinophils to extracellular matrix proteins such as fibronectin, producing a delayed efflux of eosinophils from bone marrow to peripheral blood and lungs.

Efeito do BCG na resposta alérgica à ovalbumina em camundongos geneticamente selecionados (IV-A) / The effect of BCG on the allergic response to ovalbumin in genetically selected strains of mice (IV-A)

Objetivo: Investigar se o tratamento com BCG é capaz de bloquear a resposta alergica pulmonar de camundongos geneticamente selecionados para uma boa (HIV-A) ou má resposta ( LIV-A) de anticorpos imunizados com ovalbumina ( OVA)...

To investigate whether BCG inhibits allergic pulmonary response in genetically selected mice for high (HIV-A) or low antibody response (LIV-A)...

Allergic airway inflammation inhypothyroid rats

Background: Hormones play a modulating role in allergicinflammation. Hyperthyroidism may increase the severity ofasthma, and hypothyroidism may ameliorate coexistent asthma.The mechanisms regulating this interaction are not completelyunderstood.Objective: The purpose of this study was to test the hypothesisthat thyroid hormones influence the development of allergicairway inflammation after antigen challenge in rats.Methods: The experimental design included either sensitizedor nonsensitized surgically thyroidectomized and sham-operatedrats. Experiments were performed 50 days after surgery.Thyroidectomized rats and sham-operated controls were sensitizedby subcutaneous injection of ovalbumin (OVA) andAl(OH)3 and challenged 14 days later by OVA inhalation.Bronchoalveolar lavages were performed 24 hours after challenge.Results: Compared with controls, thyroidectomized animalspresented markedly decreased cell yields from bronchoalveolarlavage fluid after OVA challenge. The impaired responsewas not related to changes in the number of circulating leukocytes.Determination of antibody serum concentrations indicatedthat thyroidectomized rats presented a marked reductionin the level of anti-OVA IgE compared with controls, withoutsignificant differences in IgG1 and IgG2a serum concentrations.Reversal of the impaired responses was attained by 16-day treatment of hypothyroid animals with thyroxine, but notby 1- or 3-day treatment.Conclusion: The data presented suggest that the continuingdeficiency of thyroid hormones influences the development ofthe inflammatory component of asthma. This is due, at least inpart, to a decrease in the production of IgE. (J Allergy ClinImmunol 1999;104:595-600.).