Histopathology of experimentally induced asthma in a murine model of sickle cell disease. Blood 2008 Sep 15;112(6):2529-38
Date
06/27/2008Pubmed ID
18579795Pubmed Central ID
PMC2532817DOI
10.1182/blood-2008-01-132506Scopus ID
2-s2.0-55249127378 (requires institutional sign-in at Scopus site) 47 CitationsAbstract
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.
Author List
Nandedkar SD, Feroah TR, Hutchins W, Weihrauch D, Konduri KS, Wang J, Strunk RC, DeBaun MR, Hillery CA, Pritchard KAAuthor
Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Anemia, Sickle CellAnimals
Asthma
Disease Models, Animal
Hemoglobins
Humans
Inflammation
Lung
Mice
Ovalbumin
Survival Rate
