Lung surfactant in a cystic fibrosis animal model

Increased alveolar phospholipid pool size without altered composition and surface tension function in cftr(m1HGU/m1HGU) mice

Wolfgang Bernhard, Jiu-Yao Wang, Thomas Tschernig, Burkhard Tümmler, Hans J. Hedrich, Horst Von Der Hardt

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background - Progressive pulmonary dysfunction is a characteristic symptom of cystic fibrosis (CF) and is associated with functional impairment and biochemical alterations of surfactant phospholipids in the airways. However, the fundamental question of whether surfactant alterations in the CF lung are secondary to the pulmonary damage or are present before initiation of chronic infection and inflammation has yet to be resolved in patients with cystic fibrosis but can now be addressed in CF mice that exhibit the basic defect in the airways. A study was therefore undertaken to investigate the pool sizes, composition, and function of lung surfactant in the non-infected cftr(m1HGU/m1HGU) mouse. Methods - The amount and composition of phospholipid classes and phosphatidylcholine molecular species were determined in bronchoalveolar lavage (BAL) fluid and lavaged lungs by high performance liquid chromatography (HPLC). Surfactant protein A (SP-A) levels in BAL fluid were determined by ELISA and surfactant for functional measurements was isolated from BAL fluid by differential ultracentrifugation. Equilibrium and minimal surface tension of surfactant was assessed by the pulsating bubble surfactometer technique. MF1, BALB/c, C57/BL6, and C3H/He mice served as controls. Results - BAL fluid of cftr(m1HGU/m1HGU) mice contained 1.02 (95% confidence interval (CI) 0.89 to 1.16) μmol phospholipid and 259 (239 to 279) ng SP-A. BAL fluid of MF1, BALB/c, C57BL/6, and G3H/He mice contained 0.69 (0.63 to 0.75), 0.50 (0.42 to 0.57), 0.52 (0.40 to 0.64), and 0.45 (0.27 to 0.63) μmol phospholipid, respectively. After correction for the different body weights of mouse strains, phospholipid levels in BAL fluid of cftr(mlHGU/mlHGU) mice were increased by 64 (52 to 76)%, 60 (39 to 89)%, 72 (45 to 113)%, and 92 (49 to 163)%, respectively, compared with controls. The amount of SP-A in BAL fluid and the composition of phospholipid as well as phosphatidylcholine molecular species in BAL fluid and lung tissue was unchanged in 1HGU/m1HGU mice compared with controls. The increase in phospholipids in BAL fluid of cftr(m1HGU/m1HGU) mice resulted from an increased fraction of large aggregates which exhibited normal surface tension function. Conclusion - In cftr(m1HGU/m1HGU) mice surfactant homeostasis is perturbed by an increased phospholipid pool in the alveolar compartment.

Original languageEnglish
Pages (from-to)723-730
Number of pages8
JournalThorax
Volume52
Issue number8
DOIs
Publication statusPublished - 1997 Jan 1

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Surface Tension
Bronchoalveolar Lavage Fluid
Cystic Fibrosis
Surface-Active Agents
Phospholipids
Animal Models
Lung
Pulmonary Surfactant-Associated Protein A
Phosphatidylcholines
Inbred C3H Mouse
Ultracentrifugation
Homeostasis
Enzyme-Linked Immunosorbent Assay
High Pressure Liquid Chromatography
Body Weight
Confidence Intervals
Inflammation

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine

Cite this

Bernhard, Wolfgang ; Wang, Jiu-Yao ; Tschernig, Thomas ; Tümmler, Burkhard ; Hedrich, Hans J. ; Von Der Hardt, Horst. / Lung surfactant in a cystic fibrosis animal model : Increased alveolar phospholipid pool size without altered composition and surface tension function in cftr(m1HGU/m1HGU) mice. In: Thorax. 1997 ; Vol. 52, No. 8. pp. 723-730.
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title = "Lung surfactant in a cystic fibrosis animal model: Increased alveolar phospholipid pool size without altered composition and surface tension function in cftr(m1HGU/m1HGU) mice",
abstract = "Background - Progressive pulmonary dysfunction is a characteristic symptom of cystic fibrosis (CF) and is associated with functional impairment and biochemical alterations of surfactant phospholipids in the airways. However, the fundamental question of whether surfactant alterations in the CF lung are secondary to the pulmonary damage or are present before initiation of chronic infection and inflammation has yet to be resolved in patients with cystic fibrosis but can now be addressed in CF mice that exhibit the basic defect in the airways. A study was therefore undertaken to investigate the pool sizes, composition, and function of lung surfactant in the non-infected cftr(m1HGU/m1HGU) mouse. Methods - The amount and composition of phospholipid classes and phosphatidylcholine molecular species were determined in bronchoalveolar lavage (BAL) fluid and lavaged lungs by high performance liquid chromatography (HPLC). Surfactant protein A (SP-A) levels in BAL fluid were determined by ELISA and surfactant for functional measurements was isolated from BAL fluid by differential ultracentrifugation. Equilibrium and minimal surface tension of surfactant was assessed by the pulsating bubble surfactometer technique. MF1, BALB/c, C57/BL6, and C3H/He mice served as controls. Results - BAL fluid of cftr(m1HGU/m1HGU) mice contained 1.02 (95{\%} confidence interval (CI) 0.89 to 1.16) μmol phospholipid and 259 (239 to 279) ng SP-A. BAL fluid of MF1, BALB/c, C57BL/6, and G3H/He mice contained 0.69 (0.63 to 0.75), 0.50 (0.42 to 0.57), 0.52 (0.40 to 0.64), and 0.45 (0.27 to 0.63) μmol phospholipid, respectively. After correction for the different body weights of mouse strains, phospholipid levels in BAL fluid of cftr(mlHGU/mlHGU) mice were increased by 64 (52 to 76){\%}, 60 (39 to 89){\%}, 72 (45 to 113){\%}, and 92 (49 to 163){\%}, respectively, compared with controls. The amount of SP-A in BAL fluid and the composition of phospholipid as well as phosphatidylcholine molecular species in BAL fluid and lung tissue was unchanged in 1HGU/m1HGU mice compared with controls. The increase in phospholipids in BAL fluid of cftr(m1HGU/m1HGU) mice resulted from an increased fraction of large aggregates which exhibited normal surface tension function. Conclusion - In cftr(m1HGU/m1HGU) mice surfactant homeostasis is perturbed by an increased phospholipid pool in the alveolar compartment.",
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Lung surfactant in a cystic fibrosis animal model : Increased alveolar phospholipid pool size without altered composition and surface tension function in cftr(m1HGU/m1HGU) mice. / Bernhard, Wolfgang; Wang, Jiu-Yao; Tschernig, Thomas; Tümmler, Burkhard; Hedrich, Hans J.; Von Der Hardt, Horst.

In: Thorax, Vol. 52, No. 8, 01.01.1997, p. 723-730.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Lung surfactant in a cystic fibrosis animal model

T2 - Increased alveolar phospholipid pool size without altered composition and surface tension function in cftr(m1HGU/m1HGU) mice

AU - Bernhard, Wolfgang

AU - Wang, Jiu-Yao

AU - Tschernig, Thomas

AU - Tümmler, Burkhard

AU - Hedrich, Hans J.

AU - Von Der Hardt, Horst

PY - 1997/1/1

Y1 - 1997/1/1

N2 - Background - Progressive pulmonary dysfunction is a characteristic symptom of cystic fibrosis (CF) and is associated with functional impairment and biochemical alterations of surfactant phospholipids in the airways. However, the fundamental question of whether surfactant alterations in the CF lung are secondary to the pulmonary damage or are present before initiation of chronic infection and inflammation has yet to be resolved in patients with cystic fibrosis but can now be addressed in CF mice that exhibit the basic defect in the airways. A study was therefore undertaken to investigate the pool sizes, composition, and function of lung surfactant in the non-infected cftr(m1HGU/m1HGU) mouse. Methods - The amount and composition of phospholipid classes and phosphatidylcholine molecular species were determined in bronchoalveolar lavage (BAL) fluid and lavaged lungs by high performance liquid chromatography (HPLC). Surfactant protein A (SP-A) levels in BAL fluid were determined by ELISA and surfactant for functional measurements was isolated from BAL fluid by differential ultracentrifugation. Equilibrium and minimal surface tension of surfactant was assessed by the pulsating bubble surfactometer technique. MF1, BALB/c, C57/BL6, and C3H/He mice served as controls. Results - BAL fluid of cftr(m1HGU/m1HGU) mice contained 1.02 (95% confidence interval (CI) 0.89 to 1.16) μmol phospholipid and 259 (239 to 279) ng SP-A. BAL fluid of MF1, BALB/c, C57BL/6, and G3H/He mice contained 0.69 (0.63 to 0.75), 0.50 (0.42 to 0.57), 0.52 (0.40 to 0.64), and 0.45 (0.27 to 0.63) μmol phospholipid, respectively. After correction for the different body weights of mouse strains, phospholipid levels in BAL fluid of cftr(mlHGU/mlHGU) mice were increased by 64 (52 to 76)%, 60 (39 to 89)%, 72 (45 to 113)%, and 92 (49 to 163)%, respectively, compared with controls. The amount of SP-A in BAL fluid and the composition of phospholipid as well as phosphatidylcholine molecular species in BAL fluid and lung tissue was unchanged in 1HGU/m1HGU mice compared with controls. The increase in phospholipids in BAL fluid of cftr(m1HGU/m1HGU) mice resulted from an increased fraction of large aggregates which exhibited normal surface tension function. Conclusion - In cftr(m1HGU/m1HGU) mice surfactant homeostasis is perturbed by an increased phospholipid pool in the alveolar compartment.

AB - Background - Progressive pulmonary dysfunction is a characteristic symptom of cystic fibrosis (CF) and is associated with functional impairment and biochemical alterations of surfactant phospholipids in the airways. However, the fundamental question of whether surfactant alterations in the CF lung are secondary to the pulmonary damage or are present before initiation of chronic infection and inflammation has yet to be resolved in patients with cystic fibrosis but can now be addressed in CF mice that exhibit the basic defect in the airways. A study was therefore undertaken to investigate the pool sizes, composition, and function of lung surfactant in the non-infected cftr(m1HGU/m1HGU) mouse. Methods - The amount and composition of phospholipid classes and phosphatidylcholine molecular species were determined in bronchoalveolar lavage (BAL) fluid and lavaged lungs by high performance liquid chromatography (HPLC). Surfactant protein A (SP-A) levels in BAL fluid were determined by ELISA and surfactant for functional measurements was isolated from BAL fluid by differential ultracentrifugation. Equilibrium and minimal surface tension of surfactant was assessed by the pulsating bubble surfactometer technique. MF1, BALB/c, C57/BL6, and C3H/He mice served as controls. Results - BAL fluid of cftr(m1HGU/m1HGU) mice contained 1.02 (95% confidence interval (CI) 0.89 to 1.16) μmol phospholipid and 259 (239 to 279) ng SP-A. BAL fluid of MF1, BALB/c, C57BL/6, and G3H/He mice contained 0.69 (0.63 to 0.75), 0.50 (0.42 to 0.57), 0.52 (0.40 to 0.64), and 0.45 (0.27 to 0.63) μmol phospholipid, respectively. After correction for the different body weights of mouse strains, phospholipid levels in BAL fluid of cftr(mlHGU/mlHGU) mice were increased by 64 (52 to 76)%, 60 (39 to 89)%, 72 (45 to 113)%, and 92 (49 to 163)%, respectively, compared with controls. The amount of SP-A in BAL fluid and the composition of phospholipid as well as phosphatidylcholine molecular species in BAL fluid and lung tissue was unchanged in 1HGU/m1HGU mice compared with controls. The increase in phospholipids in BAL fluid of cftr(m1HGU/m1HGU) mice resulted from an increased fraction of large aggregates which exhibited normal surface tension function. Conclusion - In cftr(m1HGU/m1HGU) mice surfactant homeostasis is perturbed by an increased phospholipid pool in the alveolar compartment.

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