Increased metalloproteinase activity, oxidant production, and emphysema in surfactant protein D gene-inactivated mice.

Targeted ablation of the surfactant protein D (SP-D) gene caused chronic inflammation, emphysema, and fibrosis in the lungs of SP-D (-/-) mice. Although lung morphology was unperturbed during the first 2 weeks of life, airspace enlargement was observed by 3 weeks and progressed with advancing age. Inflammation consisted of hypertrophic alveolar macrophages and peribronchiolar-perivascular monocytic infiltrates. These abnormalities were associated with increased activity of the matrix metalloproteinases, MMP2 and MMP9, and immunostaining for MMP9 and MMP12 in alveolar macrophages. Hydrogen peroxide production by isolated alveolar macrophages also was increased significantly (10-fold). SP-D plays a critical role in the suppression of alveolar macrophage activation, which may contribute to the pathogenesis of chronic inflammation and emphysema.

[1]  J. Whitsett,et al.  Surfactant protein-A enhances respiratory syncytial virus clearance in vivo. , 1999, The Journal of clinical investigation.

[2]  M. Moustaki,et al.  Deficient hydrophilic lung surfactant proteins A and D with normal surfactant phospholipid molecular species in cystic fibrosis. , 1999, American journal of respiratory cell and molecular biology.

[3]  E. Crouch.  Structure, biologic properties, and expression of surfactant protein D (SP-D). , 1998, Biochimica et biophysica acta.

[4]  Y. Kuroki,et al.  Surfactant proteins A and D: disease markers. , 1998, Biochimica et biophysica acta.

[5]  K. Reid.  Interactions of surfactant protein D with pathogens, allergens and phagocytes. , 1998, Biochimica et biophysica acta.

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

[7]  J. Whitsett,et al.  Surfactant protein-A-deficient mice are susceptible to Pseudomonas aeruginosa infection. , 1998, American journal of respiratory cell and molecular biology.

[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]  P. Ronco,et al.  Expression of hydrophilic surfactant proteins by mesentery cells in rat and man. , 1997, The Biochemical journal.

[10]  J. Wright,et al.  Immunomodulatory Functions of Surfactant , 1995, Physiological reviews.

[11]  D. Harrison,et al.  Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. , 1996, The Journal of clinical investigation.

[12]  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.

[13]  S. Abe,et al.  Decreased contents of surfactant proteins A and D in BAL fluids of healthy smokers. , 1996, Chest.

[14]  A. Tauber,et al.  Mouse surfactant protein-D. cDNA cloning, characterization, and gene localization to chromosome 14. , 1995, Journal of immunology.

[15]  Woessner Jf.  Quantification of matrix metalloproteinases in tissue samples. , 1995 .

[16]  R. Mason,et al.  Expression of pulmonary surfactant protein D in rat gastric mucosa. , 1995, American journal of respiratory cell and molecular biology.

[17]  H. Tanaka,et al.  Molecular cloning and expression of the mouse 105-kDa gelatinase cDNA. , 1993, Biochemical and Biophysical Research Communications - BBRC.

[18]  A. Persson,et al.  Developmental expression of pulmonary surfactant protein D (SP-D). , 1991, American journal of respiratory cell and molecular biology.

[19]  D. C. Sheehan,et al.  Theory and Practice of Histotechnology , 1980 .

[20]  A. Fishman.  Pulmonary Diseases and Disorders , 1980 .

[21]  B. Hill,et al.  A simple, rapid microassay for DNA , 1975, FEBS letters.

[22]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.