The respiratory tract is the target of multiple infectious agents. Because the lungs are continually exposed to infectious pathogens in inspired air, natural defense mechanisms have devolved to prevent infection. These defense mechanisms coordinate with each other to provide efficient protection against infection. As a result, pulmonary infections can be viewed not just as a consequence of exposure to a virulent pathogen but as a result of a breakdown of natural host defenses. SPLUNC1 or SPURT (secretory protein in upper respiratory tracts) is small, secreted protein that is expressed in epithelial areas of the nose, mouth, pharynx and lungs. It may be involved in host defense because it is highly homologous to bactericidal/permeability-increasing protein (BPI); a protein that mediates LPS related bacteria killing.
In this study, we established a constitutively overexpress CCSP-spurt transgenic mouse model to examine the biological function of spurt. We compared mRNA expression of CCSP-spurt in transgenic mice and their transgenic negative litermates. We determined that mRNA expression of CCSP-spurt was elevated in transgenic mice. The tissue distribution of overexpressed spurt in CCSP-spurt mice was confirmed to be only at trachea and lung and exist in no other tissues. Bronchoalveolar lavage (BAL) fluid from unchallenged CCSP-spurt mice had higher spurt concentration as was determined by ELISA and western blot. BAL from unchallenged CCSP-spurt mice also exhibited antibacterial activity. Furthermore, CCSP-spurt mice display enhanced bacterial clearance than wild-type mice after both groups of mice were challenged with aerosolized gram negative microorganisms Pseudomonas aeruginosa (PAO1) infection. BAL of CCSP-spurt mice had lower levels of proinflammatory cytokines than BAL of their wild-type littermates after the challenge with aerosolized P. aeruginosa.
Results from our studies suggest that spurt is a novel BPI-like antibacterial protein that may play a critical role in airway specific innate immunity. Further studies of this protein might have potential public health significance in providing better understanding of natural defense processes in respiratory tract.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-06062005-124641 |
| Date | 08 July 2005 |
| Creators | Lukinskiene, Lina |
| Contributors | Yuan Pu Di, Bruce Pitt, Chad Steele |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-06062005-124641/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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