Journal article
Cystic Fibrosis Pigs Develop Lung Disease and Exhibit Defective Bacterial Eradication at Birth
Science translational medicine, Vol.2(29), pp.29ra31-29ra31
04/28/2010
DOI: 10.1126/scitranslmed.3000928
PMCID: PMC2889616
PMID: 20427821
Abstract
Lung disease causes most of the morbidity and mortality in cystic fibrosis (CF). However, understanding its pathogenesis has been hindered by lack of an animal model with characteristic features of CF. To overcome this problem, we recently generated pigs with targeted
CFTR
genes. We now report that, within months of birth, CF pigs spontaneously develop hallmark features of CF lung disease including airway inflammation, remodeling, mucus accumulation, and infection. Their lungs contained multiple bacterial species, suggesting an equal opportunity host defense defect. In humans, the temporal and causal relationships between inflammation and infection have remained uncertain. To investigate these processes, we studied newborn pigs. Their lungs showed no inflammation, but were less often sterile than controls. Moreover, after intrapulmonary bacterial challenge, CF pigs failed to eradicate bacteria as effectively as wild-type pigs. These results suggest that impaired bacterial elimination is the pathogenic event that initiates a cascade of inflammation and pathology in CF lungs. Finding that CF pigs have a bacterial host defense defect within hours of birth provides an opportunity to further investigate pathogenesis and to test therapeutic and preventive strategies before secondary consequences develop.
Details
- Title: Subtitle
- Cystic Fibrosis Pigs Develop Lung Disease and Exhibit Defective Bacterial Eradication at Birth
- Creators
- David A Stoltz - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242David K Meyerholz - Department of Pathology, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Alejandro A Pezzulo - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Shyam Ramachandran - Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Mark P Rogan - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Greg J Davis - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Robert A Hanfland - Department of Surgery, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Chris Wohlford-Lenane - Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Cassie L Dohrn - Department of Pathology, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Jennifer A Bartlett - Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242George A Nelson - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Eugene H Chang - Department of Otolaryngology, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Peter J Taft - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Paula S Ludwig - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Mira Estin - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Emma E Hornick - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Janice L Launspach - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Melissa Samuel - Division of Animal Sciences University of Missouri, Columbia, Missouri 65211Tatiana Rokhlina - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Philip H Karp - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Lynda S Ostedgaard - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Aliye Uc - Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Timothy D Starner - Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Alexander R Horswill - Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Kim A Brogden - Department of Periodontics and Dows Institute for Dental Research College of Dentistry University of Iowa, Iowa City, Iowa 52242Randall S Prather - Division of Animal Sciences University of Missouri, Columbia, Missouri 65211Sandra S Richter - Department of Pathology, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Joel Shilyansky - Department of Surgery, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Paul B McCray - Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Joseph Zabner - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Michael J Welsh - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- Science translational medicine, Vol.2(29), pp.29ra31-29ra31
- DOI
- 10.1126/scitranslmed.3000928
- PMID
- 20427821
- PMCID
- PMC2889616
- NLM abbreviation
- Sci Transl Med
- ISSN
- 1946-6234
- eISSN
- 1946-6242
- Language
- English
- Date published
- 04/28/2010
- Academic Unit
- Neurology; Microbiology and Immunology; Pathology; Surgery; Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Pulmonary Medicine; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Radiation Oncology; Gastroenterology, Hepatology, Pancreatology, and Nutrition; Neurosurgery; Periodontics; Internal Medicine
- Record Identifier
- 9984013206502771
Metrics
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