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1.
Life Sci ; 77(13): 1480-92, 2005 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-15953620

RESUMO

The effect of Bacillus Calmette-Guérin (BCG) treatment in allergic pulmonary reaction was studied in mice genetically selected accordingly to a High (H-IVA) or Low (L-IVA) antibody responsiveness. Mice were immunized with ovalbumin (OVA) or OVA plus BCG. Two days after nasal antigenic challenge, seric IgE and IgG1 anti-OVA, eosinophils in pulmonary tissue, inflammatory cells in bronchoalveolar lavage and the compliance and conductance of respiratory system were evaluated. H-IVA mice were found more susceptible than L-IVA, and BCG was able to inhibit simultaneously the production of IgE, the bronchopulmonary inflammation and bronchial hyperresponsiveness in these genetically selected mice.


Assuntos
Vacina BCG/imunologia , Hiper-Reatividade Brônquica/prevenção & controle , Hipersensibilidade/prevenção & controle , Inflamação/prevenção & controle , Pulmão/imunologia , Anafilaxia Cutânea Passiva/imunologia , Animais , Ensaio de Imunoadsorção Enzimática , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Interferon gama/biossíntese , Leucócitos/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Ratos , Ratos Endogâmicos WF
2.
Biochem Pharmacol ; 68(4): 631-9, 2004 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-15276070

RESUMO

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 N(omega)-nitro-l-arginine methyl ester (l-NAME; 20mg/rat per day) for 4 weeks and sensitized with ovalbumin (OVA). In control rats, the pulmonary OVA-challenge promoted an early (24h) 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 24h 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, IgG(1) and IgG(2a) 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.


Assuntos
Medula Óssea/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Eosinófilos/efeitos dos fármacos , Hipersensibilidade/patologia , NG-Nitroarginina Metil Éster/farmacologia , Animais , Medula Óssea/fisiologia , Lavagem Broncoalveolar , Inibidores Enzimáticos/farmacologia , Eosinófilos/fisiologia , Fibronectinas/metabolismo , Expressão Gênica/efeitos dos fármacos , Hipersensibilidade/metabolismo , Imunoglobulinas/metabolismo , Pulmão/citologia , Pulmão/efeitos dos fármacos , Masculino , Doadores de Óxido Nítrico , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Ratos , Ratos Wistar
3.
Curr Allergy Asthma Rep ; 7(1): 56-61, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17504662

RESUMO

Helminths have a profound immunomodulatory effect upon the inductive and effector phases of inflammatory responses, including allergy. Several animal models of anaphylaxis have been established to investigate the mechanisms by which helminth infections or helminth-derived products interfere with the onset of allergic reactions. The focus of our studies was the immunosuppression induced by the intestinal roundworm Ascaris suum in the production of anaphylactic antibodies and the development of lung eosinophilic inflammation and hyperreactivity to its own allergens and to unrelated antigens. Thus, we identified a single protein affinity purified from the A. suum body extract, named PAS-1, which maintains all its immunosuppressive properties and promotes a significant increase in interleukin-10 production, an essential cytokine for the effectiveness of the suppressive mechanism. In addition, PAS-1 primes for regulatory T cells, which also mediate this mechanism. Therefore, this helminth molecule may be a promising target for therapeutic applications in allergic disorders.


Assuntos
Anafilaxia/tratamento farmacológico , Proteínas de Helminto/uso terapêutico , Helmintíase/imunologia , Imunossupressores/uso terapêutico , Animais , Humanos , Interleucina-10/biossíntese , Linfócitos T Reguladores/fisiologia
4.
Immunol Cell Biol ; 84(2): 138-44, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16519731

RESUMO

Helminth infections and parasite components have potent immunomodulatory effects on a host's immune system. In the present study, we investigated the effect of PAS-1, a protein component of Ascaris suum adult worms recognized by a monoclonal antibody (MAIP-1), on humoral and cell-mediated responses to a bystander antigen (ovalbumin [OVA]). MAIP-1 recognized only one of the three polypeptide chains of PAS-1, but neutralized the suppressive effect of the whole worm extract on OVA-specific antibody production. PAS-1 inhibited antibody production against a T-cell-dependent, but not a T-cell-independent, antigen in a dose-dependent way. IgM, IgG1, IgG2b, and also IgE and anaphylactic IgG1 levels were downregulated. In addition, PAS-1 inhibited OVA-specific delayed type hypersensitivity reactions in the footpad of mice, showing a potent immunosuppressive activity on both Th1 and Th2 responses that seems to be mediated by the induction of large amounts of IL-10 and IL-4. Indeed, PAS-1-specific spleen cells secreted sevenfold more IL-10 and threefold more IL-4 than OVA-specific cells in response to in vitro restimulation with the respective antigens. In conclusion, we showed that PAS-1, a single protein component from A. suum, maintains all its immunosuppressive properties.


Assuntos
Antígenos de Helmintos/imunologia , Ascaríase/imunologia , Ascaris suum/imunologia , Efeito Espectador/imunologia , Proteínas de Helminto/imunologia , Tolerância Imunológica , Animais , Anticorpos Anti-Helmínticos/imunologia , Formação de Anticorpos/imunologia , Antígenos de Helmintos/química , Antígenos de Helmintos/isolamento & purificação , Ascaris suum/química , Relação Dose-Resposta Imunológica , Regulação para Baixo/imunologia , Feminino , Proteínas de Helminto/química , Proteínas de Helminto/isolamento & purificação , Interleucina-10/imunologia , Interleucina-4/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células Th1/imunologia , Células Th2/imunologia
5.
J Allergy Clin Immunol ; 114(1): 97-104, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15241350

RESUMO

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.


Assuntos
Hiper-Reatividade Brônquica/imunologia , Eosinofilia/imunologia , Imunoglobulina G/imunologia , Inflamação/imunologia , Pneumopatias/imunologia , Anafilaxia/imunologia , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/imunologia , Quimiocina CCL11 , Quimiocinas CC/análise , Fatores Quimiotáticos de Eosinófilos/análise , Interleucina-5/análise , Pulmão/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais
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