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Effects of experimental asthma on inflammation and lung mechanics in sickle cell mice.

Pritchard KA, Feroah TR, Nandedkar SD, Holzhauer SL, Hutchins W, Schulte ML, Strunk RC, Debaun MR, Hillery CA
Am J Respir Cell Mol Biol. 2012 46 (3): 389-96

PMID: 22033263 · PMCID: PMC3326430 · DOI:10.1165/rcmb.2011-0097OC

Experimental asthma increases eosinophil and collagen deposition in the lungs of sickle cell disease (SCD) mice to a greater extent than in control mice. However, the effects of asthma on inflammation and airway physiology remain unclear. To determine effects of asthma on pulmonary inflammation and airway mechanics in SCD mice, hematopoietic stem cell transplantation was used to generate chimeric SCD and hemoglobin A mice. Experimental asthma was induced by sensitizing mice with ovalbumin (OVA). Airway mechanics were assessed using forced oscillation techniques. Mouse lungs were examined histologically and physiologically. Cytokine, chemokine, and growth factors in bronchoalveolar lavage fluid were determined by multiplex. IgE was quantified by ELISA. LDH was quantified using a colorimetric enzymatic assay. At baseline (nonsensitized), chimeric SCD mice developed hemolytic anemia with sickled red blood cells, mild leukocytosis, and increased vascular endothelial growth factor and IL-13 compared with chimeric hemoglobin A mice. Experimental asthma increased perialveolar eosinophils, plasma IgE, and bronchoalveolar lavage fluid IL-1β, IL-4, IL-6, and monocyte chemotactic protein 1 in chimeric hemoglobin A and SCD mice. IFN-γ levels were reduced in both groups. IL-5 was preferentially increased in chimeric SCD mice but not in hemoglobin A mice. Positive end-expiratory pressures and methacholine studies revealed that chimeric SCD mice had greater resistance in large and small airways compared with hemoglobin A mice at baseline and after OVA sensitization. SCD alone induces a baseline lung pathology that increases large and small airway resistance and primes the lungs to increased inflammation and airway hyperresponsiveness after OVA sensitization.

MeSH Terms (28)

Airway Resistance Anemia, Sickle Cell Animals Asthma Bronchial Hyperreactivity Bronchial Provocation Tests Bronchoalveolar Lavage Fluid Bronchoconstrictor Agents Colorimetry Cytokines Disease Models, Animal Enzyme-Linked Immunosorbent Assay Eosinophils Hemoglobin, Sickle Hemoglobin A Humans Immunoglobulin E Inflammation Mediators L-Lactate Dehydrogenase Lung Methacholine Chloride Mice Mice, Inbred C57BL Mice, Transgenic Ovalbumin Pneumonia Positive-Pressure Respiration Vascular Endothelial Growth Factor A

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