RESUMO
Increasing evidence suggests that parental allergic status, especially that of the mother, may play a unique and important role in influencing the development of fetal infant immune responses to inhaled allergens, independently of genetic predisposition. We have developed an experimental model in dogs where the offspring from allergic parents, when exposed to inhaled allergen, develop allergic sensitization and an asthmatic phenotype, whereas the offspring from non-allergic parents do not. Offspring from ragweed-sensitized (two litters, n = 10) or non-sensitized (two litters, n = 11) Beagle dogs were exposed repeatedly, by inhalation, to ragweed or filtered air (negative control) beginning within 1 week after birth. Serum levels of total immunoglobulin (Ig)E, and ragweed-specific IgE and IgG, were measured at specific time-points up to 40 weeks after birth. Cell differentials in the bronchoalveolar lavage were determined on days 1 and 4 following ragweed instillation into the offspring's lungs at 26 weeks of age. Changes in pulmonary resistance following challenge with histamine and ragweed (five breaths) were measured at 40 weeks after birth. Offspring from sensitized parents exposed to ragweed developed elevated serum total IgE and ragweed-specific IgE and IgG, and showed an increased pulmonary resistance to histamine and ragweed, and increased numbers of eosinophils in bronchoalveolar lavage. In contrast, offspring from non-sensitized parents did not exhibit this immune response. These results suggest that parental allergic sensitivity is important in the development of allergic sensitization and an asthmatic phenotype in the offspring.
Assuntos
Asma/imunologia , Troca Materno-Fetal/imunologia , Administração por Inalação , Resistência das Vias Respiratórias/imunologia , Alérgenos/administração & dosagem , Alérgenos/imunologia , Ambrosia/imunologia , Animais , Formação de Anticorpos/imunologia , Asma/sangue , Lavagem Broncoalveolar , Modelos Animais de Doenças , Cães , Eosinófilos/imunologia , Feminino , Histamina/imunologia , Imunização , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Contagem de Leucócitos/métodos , Fenótipo , Gravidez , Fatores de RiscoRESUMO
BACKGROUND: Acoustic rhinometry is a noninvasive method that uses sound waves to measure dimensions of the nasal cavity. METHODS: In this study, nasal patency was measured by acoustic rhinometry in allergic Beagle dogs sensitized to ragweed allergen. Ragweed (0.03-0.3%) or vehicle were administered intranasally in isoflurane-anesthetized dogs. RESULTS: The instillation of ragweed caused a dose-related decrease in nasal cavity volume and minimal cross-sectional area (Amin) without adverse systemic effects. Nasal cavity volume and Amin decreased within 30 minutes after instillation of the highest ragweed dose by 35.1 +/- 6.0% and 66.4 +/- 13.8%, respectively, and persisted for at least 90 minutes. Oral administration of alpha-adrenergic agonist, d-pseudoephedrine (3 mg/kg), or histamine H1 antagonist chlorpheniramine (10 mg/ kg) blocked the ragweed-induced nasal congestion. CONCLUSION: These results suggest that the canine model may be used to study upper-airway diseases such as allergic rhinitis and to evaluate the pharmacologic activity of nasal decongestants.
Assuntos
Resistência das Vias Respiratórias/efeitos dos fármacos , Ambrosia , Antialérgicos/farmacologia , Descongestionantes Nasais/farmacologia , Obstrução Nasal/tratamento farmacológico , Rinometria Acústica , Agonistas alfa-Adrenérgicos/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Clorfeniramina/farmacologia , Modelos Animais de Doenças , Cães , Efedrina/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos H1/farmacologia , Obstrução Nasal/induzido quimicamente , Obstrução Nasal/fisiopatologia , Oxigênio/sangue , Rinometria Acústica/métodosRESUMO
Episodic increases in air pollution have been associated with the exacerbation of asthma symptoms. Ultrafine particles are a component of air pollution and may be involved in causing the adverse health effects associated with high air pollution. We evaluated the effects of ultrafine particle inhalation on immune and airway responses in a beagle dog model of allergic asthma. Six allergic (ragweed sensitive) and six nonallergic dogs were exposed to ultrafine carbon particles (232.3 +/- 2.5 microg/m(3), 35.2 +/- 0.3 nm) for 1 h, followed by a challenge with vehicle (water) as a negative control. Airway resistance was measured during particle exposure and after vehicle challenge. Immune responses 3 days before and after (1 h and 1, 4, 7, and 11 days) particle exposure were assessed by measuring total immunoglobulin E (IgE) and ragweed-specific IgE and IgG in serum and bronchoalveolar lavage fluid (BALF), and cell differentials in BALF. Each dog was exposed a second time to ultrafine carbon particles (251.4 +/- 5.3 microg/m(3), 34.9 +/- 0.5 nm) for 1 h followed by a challenge with ragweed and the same measurements. Airway resistance did not change during particle exposure in any of the dogs, and ragweed-induced airway reactivity was not altered by particle exposure. Total and ragweed-specific serum IgE and total IgE in BALF were higher in allergic dogs at all time points. Particle exposure did not affect antibody levels in serum or BALF in allergic dogs. Nonallergic dogs developed specific IgG in response to multiple inhalation exposures to ragweed, but this was not associated with particle exposure. Neutrophils were elevated in BALF for all groups 1 day after particle exposure. In conclusion, despite the induction of low level inflammation in the lungs of allergic and nonallergic dogs, exposure to ultrafine carbon particles did not alter airway reactivity or immune responses.
Assuntos
Ambrosia/imunologia , Asma/imunologia , Carbono/efeitos adversos , Hipersensibilidade/imunologia , Imunização , Exposição por Inalação , Pulmão/imunologia , Animais , Formação de Anticorpos , Asma/fisiopatologia , Modelos Animais de Doenças , Cães , Hipersensibilidade/fisiopatologia , Imunoglobulina E/análise , Imunoglobulina G/análise , Tamanho da PartículaRESUMO
Epidemiologic studies suggest that children raised in homes of cigarette smokers have a higher incidence of asthma than children who are raised in homes of nonsmokers. We sought to develop an experimental model to understand the mechanisms involved. Female BALB/c mice were paired with male DO11.10 ovalbumin (OVA)-T cell receptor hemizygous (+/-) mice such that the offspring were either transgene positive (+/-) or negative (-/-). Mice were exposed to either air or mainstream cigarette smoke (100 mg/m(3) total particulate matter, 6 hours/day, 7 days/week) during pregnancy. Immediately after birth, newborn mice were exposed for 4 weeks to either air or sidestream cigarette smoke (SS; 5 mg/m(3) total particulate matter, 6 hours/day, 5 days/week) and then exposed for the following 6 weeks to either air, SS, OVA (5 mg/m(3), 6 hours/day, 5 days/week) or a combination of OVA-SS. DO11.10 +/- offspring exposed to OVA had increased airway hyperresponsiveness (AHR) to methacholine challenge, total IgE, OVA-specific IgE and IgG(1), lymphocytes, and neutrophils in bronchoalveolar lavage and perivascular and peribronchiolar inflammation. Exposure to SS alone caused a significant increase in AHR in both +/- and -/- mice. Transgene -/- mice did not exhibit AHR after OVA exposure unless it was delivered in combination with SS. When compared with OVA-only exposure, OVA-SS exposure decreased total IgE, OVA-specific IgE, and IgG(1) amounts in +/- mice. These results indicate that exposure to SS after birth enhanced AHR in offspring that are both predisposed (+/-) and nonpredisposed (-/-) to develop an allergic response to OVA, but this AHR was not associated with elevated lung eosinophilia or OVA-specific Ig amounts.
Assuntos
Eosinofilia/imunologia , Imunoglobulinas/imunologia , Hipersensibilidade Respiratória/imunologia , Fumaça/efeitos adversos , Administração por Inalação , Análise de Variância , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Modelos Animais de Doenças , Feminino , Imunoglobulina E/análise , Imunoglobulina E/imunologia , Imunoglobulina G/análise , Imunoglobulina G/imunologia , Imunoglobulinas/análise , Imuno-Histoquímica , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Fotomicrografia , Gravidez , Prenhez , Probabilidade , Hipersensibilidade Respiratória/patologiaRESUMO
Dogs with immunoglobulin E (IgE) allergy for ragweed that are sensitized by intrapulmonary exposure to ragweed can be used to study the pulmonary immune response that is important in allergic asthma. Using this model, we tested the hypothesis that T lymphocytes are activated locally in the airways shortly after allergen exposure of the lungs. The airways of six allergic dogs and three non-allergic dogs were exposed to ragweed by segmental allergen challenge (SAC). T-cell subsets and T-cell activation in blood and bronchoalveolar lavage (BAL) fluid were measured by flow cytometry before SAC and at 4, 24 and 72 hr thereafter. SAC caused a statistically significant increase in the percentage of major histocompatibility complex (MHC) class II-positive CD4 and CD8 T cells in BAL fluid and a significant increase in the mean fluorescent activity of MHC class II from 4 hr after SAC onward. This activation was significantly different from that found in cells from lung lobes challenged with saline, or from lung lobes in non-allergic dogs challenged with ragweed. The percentage of CD45RA(bright) CD8 cells increased significantly in allergic dogs after both ragweed and saline challenges. This was significantly higher than in non-allergic dogs. We conclude that T-cell activation in the airways of dogs can be measured after in vivo activation of the cells by measuring MHC class II and CD45RA expression in BAL fluid T cells. Furthermore, in allergic dogs, T cells are activated locally in the lungs within 4 hr after exposure to ragweed allergen. These results suggest a role for T lymphocytes in the development of late-phase allergic reactions in the airways.