Article

Histopathology of experimentally induced asthma in a murine model of sickle cell disease

Department of Surgery, Division of Pediatric Surgery, Medical College of Wisconsin, Blood Research Institute, Children's Research Institute, Cardiovascular Center, Milwaukee, WI 53226, USA.
Blood (Impact Factor: 10.45). 07/2008; 112(6):2529-38. DOI: 10.1182/blood-2008-01-132506
Source: PubMed

ABSTRACT

Asthma is a comorbid condition associated with increased rates of pain, acute chest syndrome, and premature death in human sickle cell disease (SCD). We developed an experimental asthma model in SCD and control mice expressing either normal human or murine hemoglobin to determine its effect on mortality and lung pathology. To induce lung inflammation, experimental mice were sensitized to ovalbumin (OVA) by subcutaneous OVA implantation (Sen), allowed 2 weeks to recover, and then divided into 2 groups, each receiving over a subsequent 10-day period the same dosage of aerosolized OVA but 2 different levels of exposure: 15 minutes (LoSen) and 30 minutes (HiSen). During recovery, 10% of SCD mice died compared with no deaths in control mice. An additional 30% of HiSen SCD mice died during aerosolization compared with 10% in LoSen SCD. Histologic indices of lung inflammation (eg, eosinophil recruitment, airway and vessel wall thickening, and immunoreactive TGFbeta and fsp-1) and bronchial alveolar lavage fluid eosinophil peroxidase activity differentially increased in sensitized mice compared with unsensitized mice. Our findings indicate SCD mice with experimentally induced asthma are more susceptible to death and pulmonary inflammation compared with control mice, suggesting that asthma contributes significantly to morbidity and mortality in SCD.

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Available from: Dorothee Weihrauch, Mar 11, 2014
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    • "This inflammation could in turn result in a propensity towards clinical asthma. Supporting this hypothesis is the documentation of increased mortality and an enhanced inflammatory response to allergens in mice with SCD and experimentally induced asthma [37]. Leukotrienes are a particularly intriguing commonality between asthma and SCD. "
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