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Blood, 15 September 2008, Vol. 112, No. 6, pp. 2529-2538.
Prepublished online as a Blood First Edition Paper on June 25, 2008; DOI 10.1182/blood-2008-01-132506.


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Submitted January 14, 2008
Accepted May 8, 2008

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

Sandhya D Nandedkar, Thomas R Feroah, William Hutchins, Dorothee Weihrauch, Kameswari S Konduri, Jingli Wang, Robert C Strunk, Michael R DeBaun, Cheryl A Hillery, and Kirkwood A Pritchard Jr*

Pediatric Surgery, Medical College of Wisconsin, Milwaukee, WI, United States
Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States
Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, United States
Pediatrics, Washington University in St. Louis, St. Louis, MO, United States
Pediatrics, Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI, United States

* Corresponding author; email: kpritch{at}mcw.edu.

Asthma is a co-morbid 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 wks 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 min (LoSen) and 30 min (HiSen). During recovery, 10% of SCD mice died compared to no deaths in control mice. An additional 30% of HiSen SCD mice died during aerosolization compared to 10% in LoSen SCD. Histological indices of lung inflammation (e.g., eosinophil recruitment, airway and vessel wall thickening, immunoreactive TGF{beta} and fsp-1) and bronchial alveolar lavage fluid eosinophil peroxidase activity differentially increased in sensitized mice compared to unsensitized mice. Our findings indicate SCD mice with experimentally-induced asthma are more susceptible to death and pulmonary inflammation compared to control mice suggesting that asthma contributes significantly to morbidity and mortality in SCD.


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