Pulmonary Immunity to Ragweed in a Beagle Dog Model of Allergic Asthma

Abstract

To create an allergy model in the dog, allergic Beagles with high levels of serum immunoglobulin E (IgE) and eosinophilia were bred; resulting puppies were sensitized to ragweed by intraperitoneal (IP) injection within 24 hours of birth through 22 weeks of age. At least 50% of the puppies developed high levels of serum IgE and eosinophilia. As young adults, 6 of these dogs, and 6 control age-matched, nonallergic, nonimmunized dogs were exposed by inhalation to ragweed twice at 13-day intervals, and a third time 45 days later. Total and ragweed-specific serum IgE and ragweed-specific serum IgG were increased significantly in allergic dogs relative to baseline. Allergic dogs had significantly greater levels of antibody specific for ragweed, as well as higher eosinophil counts in the bronchoalveolar lavage fluid, compared to nonallergic dogs. Airway reactivity to histamine in allergic, but not nonallergic dogs, increased significantly after aerosol exposure to ragweed. After a third exposure to ragweed, airway responses to histamine were elevated in the allergic dogs and remained high for at least 5 months. These results demonstrate the potential of the allergic dog model for investigating the underlying pulmonary immune mechanisms and therapeutic treatment of allergic asthma.

Animal Models of Allergic Diseases

“…Although an increase in eosinophils have been identified in the airways of allergic dogs, this does not seem to be associated with an increase in responsiveness of the airways probably due to the significant anatomical difference of dogs with the other species; proportionally larger airways and less prone to bronchoconstriction [145]. Nevertheless, anatomical and clinical differences are evident between dogs and people; such model has been largely used due to the unique ability of dogs to show persistent sensitization (prolonged airways hyperresponsiveness) up to 5 months post challenge with A. suum [146]. The main drawback for this model is that dogs are labor intense and expensive, but these difficulties are easily overridden by the usefulness of such model to identify pathomechanisms and long term pulmonary changes related to the asthmatic disease [134].…”

Local T‐cell activation after segmental allergen challenge in the lungs of allergic dogs

“…Serum levels of immunoglobulins were measured as described previously. 3 At the time of the study the serum levels were as follows: allergic dogs and non-allergic dogs: total IgE, 52t10 (meantSEM) and 44t22 au/ml (arbitrary units); IgE anti-ragweed, 22t5 and 3t3 au/ml; IgG anti-ragweed 133t38 and 62t11 au/ml, respectively.…”

“…3,16 Six dogs were sensitized by regular intraperitoneal or subcutaneous injections with ragweed (ragweed short, Ambrosia artemisiifolia, Bayer, Emeryville, CA) and aluminium hydroxide as adjuvant. 3 Furthermore, a single dose of ragweed was instilled into six different lung lobes of each dog via a bronchoscope 4 -8 months before the experiments. Three dogs not previously exposed to ragweed were used as non-allergic controls.…”

“…The dogs develop bronchial hyper-reactivity, and upon re-exposure of the airways to ragweed, local inflammatory reactions occur that are characterized by histamine release and a rapid increase of neutrophilic granulocytes in the lungs, followed by a local increase of eosinophilic granulocytes and lymphocytes. 3,4 Furthermore, the bronchoalveolar lavage (BAL) fluid of allergen-exposed dogs contains soluble factors that induce increased secretion of mucin in in vitro cultures of airway epithelial cells. 5 Thus, the characteristics of these dogs make them an excellent animal model for the study of the allergic pulmonary immunity that is important in asthma.…”

“…[1][2][3] The intrapulmonary deposition of ragweed in sensitized allergic dogs results in pulmonary sensitization. The dogs develop bronchial hyper-reactivity, and upon re-exposure of the airways to ragweed, local inflammatory reactions occur that are characterized by histamine release and a rapid increase of neutrophilic granulocytes in the lungs, followed by a local increase of eosinophilic granulocytes and lymphocytes.…”