Asthma Progression to Airway Remodeling and Bone Marrow Eosinophil Responses in Genetically Distinct Strains of Mice

Details

• Personal Author:
  Hogan MB ; Hubbs, Ann F. ; Landreth KS ; McPherson LE ; Piktel D
• Description:
  Background: patient factors that cause long-term airway remodeling are largely unidentified. This Suggests that genetic differences may determine which asthmatic patients develop airway remodeling. A murine model with repeated allergen exposure leading to peribronchial fibrosis in complement factor 5 (C5)-deficient A/J mice has been used to study asthma progression. No Studies have addressed the systemic effects of allergen sensitization or chronic allergen exposure on bone marrow eosinophilopoiesis in this mouse strain. Objective: to investigate bone marrow eosinophil responses during acute sensitization and chronic allergen exposure using genetically distinct mouse strains differing in persistent airway reactivity and remodeling. Methods: the C5-sufficient BALB/c and C5-deficient A/J mice were repetitively exposed to intranasal ovalbumin for 12 weeks. Subsequently, the mice were evaluated for airway eosinophilia, mucus-containing goblet cells, and peribronchial fibrosis. Both strains of mice were also acutely sensitized to ovalbumin. Bone marrow eosinophil progenitor cells and mature eosinophils were enumerated. Results: BALB/c and A/J mice have similar bone marrow responses after acute allergen exposure, with elevations in bone marrow eosinophil progenitor cell and eosinophil numbers. After chronic allergen exposure, only C5-deficient A/J mice that developed peribronchial fibrosis exhibited bone marrow eosinophilia. BALB/c mice lacked peribronchial fibrosis and extinguished accelerated eosinophil production after long-term allergen challenge. Conclusions: chronic airway remodeling after repeated allergen exposure in genetically different mice correlated with differences in long-term bone marrow eosinophilopoiesis. Preventing asthma from progressing to chronic airway remodeling with fibrosis may involve identifying genetically determined influences on bone marrow responses to chronic allergen exposure. [Description provided by NIOSH]
• Subjects:
  Air Pollution Air Pollution, Indoor Antibodies Antigens Asthma Asthma, Occupational Genetics Hypersensitivity Immune System Laboratories Lung Musculoskeletal System Occupational Health Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Air-quality Airway-obstruction Allergic-disorders Allergies Antibody-response Bone-marrow Breathing Breathing-zone Bronchial-asthma Genetic-factors Immune-reaction Immune-system-disorders Laboratory-animals Laboratory-testing Lung-irritants Pulmonary-system-disorders

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• ISSN:
  1081-1206
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Nevada ; OSHA Region 3 ; OSHA Region 9 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  101
• Issue:
  6
• NIOSHTIC Number:
  nn:20034872
• Citation:
  Ann Allergy Asthma Immunol 2008 Dec; 101(6):619-625
• Contact Point Address:
  Mary Beth Hogan, University of Nevada, School of Medicine, Department of Pediatrics, 343 Elm St,Ste 201, Reno, NV 89503
• Email:
  mbhogam@medicine.nevada.edu
• Federal Fiscal Year:
  2009
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Annals of Allergy, Asthma and Immunology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:62dfcdc964355004ab6ace74a3f5de6eec378d65ee1784354182733ef52415ccb516a6c034dccc149f05599fc2e396e47fce63e0dc8625dd11c0f5e3ffdeed9c
• Download URL:
  https://stacks.cdc.gov/view/cdc/186918/cdc_186918_DS1.pdf
• File Type:
  [PDF - 266.89 KB ]