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Histopathology of experimentally induced asthma in a murine model of sickle cell disease. Blood 2008 Sep 15;112(6):2529-38

Date

06/27/2008

Pubmed ID

18579795

Pubmed Central ID

PMC2532817

DOI

10.1182/blood-2008-01-132506

Scopus ID

2-s2.0-55249127378   41 Citations

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.

Author List

Nandedkar SD, Feroah TR, Hutchins W, Weihrauch D, Konduri KS, Wang J, Strunk RC, DeBaun MR, Hillery CA, Pritchard KA

Authors

Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin
Dorothee Weihrauch DVM, PhD Professor in the Anesthesiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Anemia, Sickle Cell
Animals
Asthma
Disease Models, Animal
Hemoglobins
Humans
Inflammation
Lung
Mice
Ovalbumin
Survival Rate
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a