Reproducibility of a novel model of murine asthma-like pulmonary inflammation

Abstract

SUMMARYSensitization to cockroach allergens (CRA) has been implicated as a major cause of asthma, especially among inner-city populations. Endotoxin from Gram-negative bacteria has also been investigated for its role in attenuating or exacerbating the asthmatic response. We have created a novel model utilizing house dust extract (HDE) containing high levels of both CRA and endotoxin to induce pulmonary inflammation (PI) and airway hyperresponsiveness (AHR). A potential drawback of this model is that the HDE is in limited supply and preparation of new HDE will not contain the exact components of the HDE used to define our model system. The present study involved testing HDEs collected from various homes for their ability to cause PI and AHR. Dust collected from five homes was extracted in phosphate buffered saline overnight. The levels of CRA and endotoxin in the supernatants varied from 7·1 to 49·5 mg/ml of CRA and 1·7-6 m g/ml of endotoxin in the HDEs. Following immunization and two pulmonary exposures to HDE all five HDEs induced AHR, PI and plasma IgE levels substantially higher than normal mice. This study shows that HDE containing high levels of cockroach allergens and endotoxin collected from different sources can induce an asthma-like response in our murine model.

Assessing Pulmonary Pathology by Detailed Examination of Respiratory Function

“…6,7,35,36 Our results parallel those of Campbell et al 7 in that we observed significant accumulation of eosinophils, neutrophils and lymphocytes in the airways, a space normally populated solely by macrophages such that the presence of inflammatory cells indicates a pathological process. Corticosteroids are an integral component of the standard asthma controller therapies and have been widely used for decades.…”

“…CRA is a highly potent allergen (robust immunization is achieved with a dose thousands of times less than that required for Ova) and does not require an adjuvant for sensitization. 6,7 Campbell et al 7 established the first CRA induced model of asthma in mice and demonstrated robust pulmonary inflammation with many asthma-like features. The complex nature of this allergen and its close correspondence with its urban environmental counterpart makes this model highly applicable to the study of human disease.…”

Multiple exposures to swine barn air induce lung inflammation and airway hyper-responsiveness

“…It is likely that high levels of endotoxin in the barn air observed in our study are partially contributing to lung dysfunction induced in the exposed rats. Endotoxin in house dust has also been identified as a cause of lung dysfunction, which is characterized by increased AHR and inflammation [25]. Notwithstanding the cause of AHR following exposure to the highly complex barn air, there was amelioration of AHR in rats exposed for 20 days in conjunction with persistent inflammation.…”

The pulmonary and hepatic immune microenvironment and its contribution to the early systemic inflammation following blunt chest trauma

“…Intratracheal delivery of agents was performed as described previously (27,28). Mice were anesthetized lightly with sevoflurane and restrained in supine position with their head reclined.…”