Altered stability of pulmonary surfactant in SP-C-deficient mice

The surfactant protein C (SP-C) gene encodes an extremely hydrophobic, 4-kDa peptide produced by alveolar epithelial cells in the lung. To discern the role of SP-C in lung function, SP-C-deficient (−/−) mice were produced. The SP-C (−/−) mice were viable at birth and grew normally to adulthood without apparent pulmonary abnormalities. SP-C mRNA was not detected in the lungs of SP-C (−/−) mice, nor was mature SP-C protein detected by Western blot of alveolar lavage from SP-C (−/−) mice. The levels of the other surfactant proteins (A, B, D) in alveolar lavage were comparable to those in wild-type mice. Surfactant pool sizes, surfactant synthesis, and lung morphology were similar in SP-C (−/−) and SP-C (+/+) mice. Lamellar bodies were present in SP-C (−/−) type II cells, and tubular myelin was present in the alveolar lumen. Lung mechanics studies demonstrated abnormalities in lung hysteresivity (a term used to reflect the mechanical coupling between energy dissipative forces and tissue-elastic properties) at low, positive-end, expiratory pressures. The stability of captive bubbles with surfactant from the SP-C (−/−) mice was decreased significantly, indicating that SP-C plays a role in the stabilization of surfactant at low lung volumes, a condition that may accompany respiratory distress syndrome in infants and adults.

[1]  F. Askin,et al.  A mutation in the surfactant protein C gene associated with familial interstitial lung disease. , 2001, The New England journal of medicine.

[2]  P. Germann,et al.  Effect of recombinant SP-C surfactant in a porcine lavage model of acute lung injury. , 2000, Journal of applied physiology.

[3]  R. Spragg,et al.  Dosing and delivery of a recombinant surfactant in lung-injured adult sheep. , 1999, American journal of respiratory and critical care medicine.

[4]  T. Weaver,et al.  Synthesis, processing and secretion of surfactant proteins B and C. , 1998, Biochimica et biophysica acta.

[5]  J. Johansson,et al.  Structure and properties of surfactant protein C. , 1998, Biochimica et biophysica acta.

[6]  S. Schürch,et al.  Formation and structure of surface films: captive bubble surfactometry. , 1998, Biochimica et biophysica acta.

[7]  Susan E. Wert,et al.  Surfactant Protein-D Regulates Surfactant Phospholipid Homeostasis in Vivo * , 1998, The Journal of Biological Chemistry.

[8]  C. Epstein,et al.  Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein D. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[9]  H. Galla,et al.  The role of pulmonary surfactant protein C during the breathing cycle , 1998 .

[10]  P. Germann,et al.  Effects of rSP-C surfactant on oxygenation and histology in a rat-lung-lavage model of acute lung injury. , 1998, American journal of respiratory and critical care medicine.

[11]  C. Rodrigo,et al.  Inhaled flunisolide for acute severe asthma. , 1998, American journal of respiratory and critical care medicine.

[12]  A. Jobe,et al.  Lung function in premature lambs and rabbits treated with a recombinant SP-C surfactant. , 1998, American journal of respiratory and critical care medicine.

[13]  H. Haagsman,et al.  The Pulmonary Surfactant System: Biochemical and Clinical Aspects , 1997, Lung.

[14]  B. Stripp,et al.  Altered surfactant function and structure in SP-A gene targeted mice. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[15]  K. Yukitake,et al.  Lung function in premature rabbits treated with recombinant human surfactant protein-C. , 1996, American journal of respiratory and critical care medicine.

[16]  B. Stripp,et al.  Targeted disruption of the surfactant protein B gene disrupts surfactant homeostasis, causing respiratory failure in newborn mice. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[17]  J. Whitsett,et al.  Temporal-spatial distribution of SP-B and SP-C proteins and mRNAs in developing respiratory epithelium of human lung. , 1994, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[18]  J. Whitsett,et al.  Lipid effects on aggregation of pulmonary surfactant protein SP-C studied by fluorescence energy transfer. , 1993, Biochemistry.

[19]  J. Whitsett,et al.  Transcriptional elements from the human SP-C gene direct expression in the primordial respiratory epithelium of transgenic mice. , 1993, Developmental biology.

[20]  A. Jobe,et al.  Pulmonary surfactant therapy. , 1993, The New England journal of medicine.

[21]  H. Colten,et al.  Brief report: deficiency of pulmonary surfactant protein B in congenital alveolar proteinosis. , 1993, The New England journal of medicine.

[22]  Robert B. Darling,et al.  Effects of low work function metals on the barrier height of sulfide‐treated n‐type GaAs(100) , 1992 .

[23]  J. Whitsett,et al.  Effects of lung surfactant proteolipid SP-C on the organization of model membrane lipids: a fluorescence study. , 1992, Biochimica et biophysica acta.

[24]  J. Fredberg,et al.  Input impedance and peripheral inhomogeneity of dog lungs. , 1992, Journal of applied physiology.

[25]  J. Whitsett,et al.  Tumor necrosis factor-alpha inhibits expression of pulmonary surfactant protein. , 1990, The Journal of clinical investigation.

[26]  F. Possmayer,et al.  Role of bovine pulmonary surfactant-associated proteins in the surface-active property of phospholipid mixtures. , 1990, Biochimica et biophysica acta.

[27]  R. Notter,et al.  Hydrophobic Surfactant-Associated Protein in Whole Lung Surfactant and Its Importance for Biophysical Activity in Lung Surfactant Extracts Used for Replacement Therapy , 1986, Pediatric Research.