Effects of Experimental Asthma on Inflammation and Lung Mechanics in Sickle Cell Mice
| Autor: | William Hutchins, Sandra L. Holzhauer, Thom R. Feroah, Michael R. DeBaun, S.D. Nandedkar, Cheryl A. Hillery, Robert C. Strunk, Marie L. Schulte, Kirkwood A. Pritchard |
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| Rok vydání: | 2012 |
| Předmět: |
Vascular Endothelial Growth Factor A
Hemolytic anemia Hemoglobin Sickle Clinical Biochemistry Immunoglobulin E Bronchoconstrictor Agents Positive-Pressure Respiration Mice Airway resistance Lung Methacholine Chloride medicine.diagnostic_test biology Hemoglobin A Articles respiratory system medicine.anatomical_structure Cytokines Colorimetry Bronchial Hyperreactivity Inflammation Mediators medicine.symptom Bronchoalveolar Lavage Fluid Pulmonary and Respiratory Medicine Ovalbumin Enzyme-Linked Immunosorbent Assay Mice Transgenic Inflammation Anemia Sickle Cell Bronchial Provocation Tests medicine Animals Humans Molecular Biology Interleukin 5 L-Lactate Dehydrogenase business.industry Airway Resistance Pneumonia Cell Biology Eosinophil medicine.disease Asthma respiratory tract diseases Eosinophils Mice Inbred C57BL Disease Models Animal Bronchoalveolar lavage Immunology biology.protein business |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 46:389-396 |
| ISSN: | 1535-4989 1044-1549 |
| DOI: | 10.1165/rcmb.2011-0097oc |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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