and specific aims): This application seeks to determine the role and the mechanism by which surfactant protein-A (SP-A) protects the lung from bacterial infection. SP-A is an abundant surfactant associated protein produced postnatally principally by two cellular compartments, the distal bronchiolar epithelium and alveolar Type II cells and the tracheal/bronchial glands. Its structural and functional resemblance to collections and the in vitro properties as an opsonin of bacterial pathogens strongly infer that SP-A is an important component of the innate immune system of the lung. This application, will test the hypothesis that SP-A protects the lung in vivo from bacterial infection and reduces septic spread from the lung by enhancing bacterial uptake and killing by alveolar macrophages and peripheral monocytes.
The specific aims address: 1) the role and mechanism of SP-A during lung infection and prevention of septic spread of bacteria; 2) cellular sites and quantity of SP-A synthesis required to protect the lungs from bacterial infection; and protection of the lung of SP-A -/- mice from infection by transtracheal replacement with SP-A.
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| Deshmukh, Hitesh S; McLachlan, Anne; Atkinson, Jeffrey J et al. (2009) Matrix metalloproteinase-14 mediates a phenotypic shift in the airways to increase mucin production. Am J Respir Crit Care Med 180:834-45 |
| Kramer, Elizabeth L; Mushaben, Elizabeth M; Pastura, Patricia A et al. (2009) Early growth response-1 suppresses epidermal growth factor receptor-mediated airway hyperresponsiveness and lung remodeling in mice. Am J Respir Cell Mol Biol 41:415-25 |
| Korfhagen, Thomas R; Le Cras, Timothy D; Davidson, Cynthia R et al. (2009) Rapamycin prevents transforming growth factor-alpha-induced pulmonary fibrosis. Am J Respir Cell Mol Biol 41:562-72 |
| Glasser, Stephan W; Witt, Teah L; Senft, Albert P et al. (2009) Surfactant protein C-deficient mice are susceptible to respiratory syncytial virus infection. Am J Physiol Lung Cell Mol Physiol 297:L64-72 |
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| Hardie, William D; Davidson, Cynthia; Ikegami, Machiko et al. (2008) EGF receptor tyrosine kinase inhibitors diminish transforming growth factor-alpha-induced pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 294:L1217-25 |
| Glasser, Stephan W; Senft, Albert P; Whitsett, Jeffrey A et al. (2008) Macrophage dysfunction and susceptibility to pulmonary Pseudomonas aeruginosa infection in surfactant protein C-deficient mice. J Immunol 181:621-8 |
| Senft, Albert P; Korfhagen, Thomas R; Whitsett, Jeffrey A et al. (2007) Surfactant protein D regulates the cell surface expression of alveolar macrophage beta(2)-integrins. Am J Physiol Lung Cell Mol Physiol 292:L469-75 |
| Berclaz, Pierre-Yves; Carey, Brenna; Fillipi, Marie-Dominique et al. (2007) GM-CSF regulates a PU.1-dependent transcriptional program determining the pulmonary response to LPS. Am J Respir Cell Mol Biol 36:114-21 |
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