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Effects of experimental asthma on inflammation and lung mechanics in sickle cell mice. Am J Respir Cell Mol Biol 2012 Mar;46(3):389-96

Date

10/29/2011

Pubmed ID

22033263

Pubmed Central ID

PMC3326430

DOI

10.1165/rcmb.2011-0097OC

Scopus ID

2-s2.0-84857746097   22 Citations

Abstract

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.

Author List

Pritchard KA Jr, Feroah TR, Nandedkar SD, Holzhauer SL, Hutchins W, Schulte ML, Strunk RC, Debaun MR, Hillery CA

Author

Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin




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

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 A
Hemoglobin, Sickle
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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