homeostasis/metabolism
• BALF from LPS-challenged mutants but not from challenged wild-type shows that a rapid and transient increase in levels of Tnfa (TNF alpha) occurs
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• an exaggerated induction of MMP-2 and -9 activity is found in BALF from LPS-challenged mutants; serine protease activity is also elevated
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respiratory system
• lungs are consistently characterized by increased cellularity within the parenchyma
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• there are large macrophages in mutant lungs despite specific pathogen-free (SPF) housing
• alveolar macrophages are frequently vacuolated with eosinophilic cytoplasm
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• lungs have areas of infiltration into the interstitium and alveoli at 3-4 months of age and older
• lungs are characterized by areas of accumulation of mononuclear inflammatory cells around airways and blood vessels
• areas of pulmonary consolidations become evident around 5-6 weeks of age and progress from that point
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• in rare cases, pulmonary adenocarcinomas are detected in mice approaching 2 years of age
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• alveolar spaces contain eosinophilic matter accompanied by degranulated eosinophilic protein
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atelectasis
(
J:111432
)
• in 3-4 month-old and older mutants, lungs show areas of atelectasis
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• lungs show some areas of enlarged airspaces at 3-4 months of age and older
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• excessive fibrotic deposits of extracellular matrix in the alveolar septa
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• lungs display signs of fibrosis characterized by depostion of extracellular matrix material in the alveolar septa
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• epithelial cells lining the conducting airways exhibit extensive mucus cell metaplasia resulting in mucus aggregates in the airway lumen
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• epithelium lining conducting airways is frequently hypertrophic and many epithelial cells are enlarged due to excessive production/accumulation of mucus material
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• mutants show decreased tissue elastance of the lung tissue at baseline compared with wild-type
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• aging mice show signs of respiratory distress, evident by use of accessory muscles
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hematopoietic system
• eosinophils are most prominent cell type in infiltrates in lungs (30% of total bronchoalveolar lavage fluid (BALF) from mutants compared to 2% in wild-type
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• there are large macrophages in mutant lungs despite specific pathogen-free (SPF) housing
• alveolar macrophages are frequently vacuolated with eosinophilic cytoplasm
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• engulfed crystalline eosinophilic material is often observed in macrophages in mutant lungs
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immune system
• eosinophils are most prominent cell type in infiltrates in lungs (30% of total bronchoalveolar lavage fluid (BALF) from mutants compared to 2% in wild-type
|
• there are large macrophages in mutant lungs despite specific pathogen-free (SPF) housing
• alveolar macrophages are frequently vacuolated with eosinophilic cytoplasm
|
• mutants have enhanced pulmonary innate immune response to LPS challenge
• extent of neutrophilic accumulation in BAL-F of LPS-challenged wild-type mice is 3-fold higher than mutants but number of eosinophils and macrophages (~1/3 of total cells) in BALF from unchallenged mutants are profoundly elevated compared to unchallenged wild-type
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• engulfed crystalline eosinophilic material is often observed in macrophages in mutant lungs
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• BALF from LPS-challenged mutants but not from challenged wild-type shows that a rapid and transient increase in levels of Tnfa (TNF alpha) occurs
|
• BALF from mutant lungs have elevated levels of IL-5 compared to wild-type (70 pg/ml vs 17 pg/ml)
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• lungs have areas of infiltration into the interstitium and alveoli at 3-4 months of age and older
• lungs are characterized by areas of accumulation of mononuclear inflammatory cells around airways and blood vessels
• areas of pulmonary consolidations become evident around 5-6 weeks of age and progress from that point
|
neoplasm
• in rare cases, pulmonary adenocarcinomas are detected in mice approaching 2 years of age
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growth/size/body
• lungs are consistently characterized by increased cellularity within the parenchyma
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