DOES LACK OF Cftr GENE LEAD TO DEVELOPMENTAL ABNORMALITIES IN THE LUNG?

Geiser, Marianne; Zimmermann, Beat; Baumann, Markus; Cruz‐Orive, Luis M.

doi:10.1080/019021400750048090

Cited by 15 publications

(10 citation statements)

References 15 publications

(24 reference statements)

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“…Also in agreement with the above mentioned morphological studies [22,23], we found no statistically significant differences in any of the lung structure parameters analyzed between Cftr mutant and WT mice. The lung tissue content in Cftr mutant mice was 15.0 ± 4.2% (range 12.4 – 19.8%).…”

Section: Resultssupporting

confidence: 93%

“…Overall, we have no indications for microstructural changes of the peripheral lung, which is in agreement with our previous findings [22,23]. While lung and airway volumes as well as gas exchange capacity were not affected by the mutation, we found moderate changes in lung resistance and compliance.…”

Section: Discussionsupporting

confidence: 93%

“…In general, body weight (BW) was lower in females than in males, but comparable among Cftr mutant and WT mice. In accordance with morphological studies [22,23], the mutation had no effect on lung size (TLC, total lung capacity), both, for absolute values and when expressed in relation to BW (TLC/BW). Similarly, the conducting airway volume (VD, series dead space volume) and its relative proportion to lung size (VD/TLC), as well as the gas exchanging capacity across the alveolar capillary membrane (D CO , diffusing capacity for carbon monoxide CO) were not altered, the latter also not when accounting for the alveolar volume (VA, D CO /VA).…”

Section: Resultssupporting

confidence: 88%

“…Although these mice – like most other CF mouse models – do not develop lung disease spontaneously, Cftr tm1HGU mice develop pathogen-specific lung disease after bacterial challenge; they are more easily infected and develop more severe lung pathology than non- cf mice [34]. Uninfected Cftr tm1HGU mice have a normal fine pulmonary structure including the lung lining layer [22,23]. …”

Section: Methodsmentioning

confidence: 99%

“…To analyze the distribution of inhaled TiO 2 NP in lung cells at the individual particle level, organs were fixed in situ by instillation of phosphate-buffered 2.5% glutaraldehyde (350 mOsm, pH 7.4) at a pressure of 20 - 25 cm H 2 O as described previously [22]. Thereafter, lungs were removed in toto from the thorax and stored for at least 24 h in fixative solution at 4°C.…”

Section: Methodsmentioning

confidence: 99%

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Biokinetics of nanoparticles and susceptibility to particulate exposure in a murine model of cystic fibrosis

et al. 2014

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BackgroundPersons with cystic fibrosis (CF) are at-risk for health effects from ambient air pollution but little is known about the interaction of nanoparticles (NP) with CF lungs. Here we study the distribution of inhaled NP in a murine CF model and aim to reveal mechanisms contributing to adverse effects of inhaled particles in susceptible populations.MethodsChloride channel defective CftrTgH (neoim) Hgu mice were used to analyze lung function, lung distribution and whole body biokinetics of inhaled NP, and inflammatory responses after intratracheal administration of NP. Distribution of 20-nm titanium dioxide NP in lungs was assessed on ultrathin sections immediately and 24 h after a one-hour NP inhalation. NP biokinetics was deduced from total and regional lung deposition and from whole body translocation of inhaled 30-nm iridium NP within 24 h after aerosol inhalation. Inflammatory responses were assessed within 7 days after carbon NP instillation.ResultsCftr mutant females had moderately reduced lung compliance and slightly increased airway resistance compared to wild type mice. We found no genotype dependent differences in total, regional and head deposition or in secondary-organ translocation of inhaled iridium NP. Titanium dioxide inhalation resulted in higher NP uptake by alveolar epithelial cells in Cftr mutants. Instillation of carbon NP induced a comparable acute and transient inflammatory response in both genotypes. The twofold increase of bronchoalveolar lavage (BAL) neutrophils in Cftr mutant compared to wild type mice at day 3 but not at days 1 and 7, indicated an impaired capacity in inflammation resolution in Cftr mutants. Concomitant to the delayed decline of neutrophils, BAL granulocyte-colony stimulating factor was augmented in Cftr mutant mice. Anti-inflammatory 15-hydroxyeicosatetraenoic acid was generally significantly lower in BAL of Cftr mutant than in wild type mice.ConclusionsDespite lacking alterations in lung deposition and biokinetics of inhaled NP, and absence of significant differences in lung function, higher uptake of NP by alveolar epithelial cells and prolonged, acute inflammatory responses to NP exposure indicate a moderately increased susceptibility of lungs to adverse effects of inhaled NP in Cftr mutant mice and provides potential mechanisms for the increased susceptibility of CF patients to air pollution.

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Section: Resultssupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

Section: Resultssupporting

confidence: 88%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Biokinetics of nanoparticles and susceptibility to particulate exposure in a murine model of cystic fibrosis

et al. 2014

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Structure and Composition of Pulmonary Arteries, Capillaries, and Veins

Townsley¹

2012

Comprehensive Physiology

242

204

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The pulmonary vasculature is comprised of three anatomic compartments connected in series: the arterial tree, an extensive capillary bed, and the venular tree. Although in general this vasculature is thin-walled, structure is nonetheless complex. Contributions to structure (and thus potentially to function) from cells other than endothelial and smooth muscle cells as well as those from the extracellular matrix should be considered. This review is multifaceted, bringing together information regarding 1) classification of pulmonary vessels, 2) branching geometry in the pulmonary vascular tree, 3) a quantitative view of structure based on morphometry of the vascular wall, 4) the relationship of nerves, a variety of interstitial cells, matrix proteins, and striated myocytes to smooth muscle and endothelium in the vascular wall, 5) heterogeneity within cell populations and between vascular compartments, 6) homo- and heterotypic cell-cell junctional complexes, and 7) the relation of the pulmonary vasculature to that of airways. These issues for pulmonary vascular structure are compared, when data is available, across species from human to mouse and shrew. Data from studies utilizing vascular casting, light and electron microscopy, as well as models developed from those data, are discussed. Finally, the need for rigorous quantitative approaches to study of vascular structure in lung is highlighted.

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Evolution and Functional Differentiation of the Diaphragm Muscle of Mammals

Fogarty¹,

Sieck²

2019

Comprehensive Physiology

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Symmorphosis is a concept of economy of biological design, whereby structural properties are matched to functional demands. According to symmorphosis, biological structures are never over designed to exceed functional demands. Based on this concept, the evolution of the diaphragm muscle (DIAm) in mammals is a tale of two structures, a membrane that separates and partitions the primitive coelomic cavity into separate abdominal and thoracic cavities and a muscle that serves as a pump to generate intra-abdominal (P ab ) and intra-thoracic (P th ) pressures. The DIAm partition evolved in reptiles from folds of the pleural and peritoneal membranes that was driven by the biological advantage of separating organs in the larger coelomic cavity into separate thoracic and abdominal cavities, especially with the evolution of aspiration breathing. The DIAm pump evolved from the advantage afforded by more effectively generation of both a negative P th for ventilation of the lungs and a positive P ab for venous return of blood to the heart and expulsive behaviors such as airway clearance, defecation, micturition, and child birth. Didactic SynopsisThe DIAm separates abdominal and thoracic cavities; thus, it is a partition, and its evolution reflects that important role in isolating organs into separate thoracic and abdominal cavities. However, the DIAm is also a muscle, and is most often described as the principal pump muscle of inspiration. However, the DIAm also serves as a pump for generating both negative P th and positive P ab in other motor behaviors. Accordingly, the evolution of the DIAm is more complex and should be considered in the context of its dual physiological roles as a partition and muscular pump. In considering DIAm evolution, we adopt the guiding concept of symmorphosis or economy of design, where biological structures are not over designed for their functional roles. Thus, this is a tale of the evolution of two diaphragms, a partition and a muscular pump that separates thoracic and abdominal cavities but also affects generation of P th and P ab .

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DOES LACK OF Cftr GENE LEAD TO DEVELOPMENTAL ABNORMALITIES IN THE LUNG?

Cited by 15 publications

References 15 publications

Biokinetics of nanoparticles and susceptibility to particulate exposure in a murine model of cystic fibrosis

Biokinetics of nanoparticles and susceptibility to particulate exposure in a murine model of cystic fibrosis

Structure and Composition of Pulmonary Arteries, Capillaries, and Veins

Evolution and Functional Differentiation of the Diaphragm Muscle of Mammals

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