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FUNCTIONAL CHARACTERIZATION OF SPURT USING TRANSGENIC MOUSE MODEL

Lukinskiene, Lina (2005) FUNCTIONAL CHARACTERIZATION OF SPURT USING TRANSGENIC MOUSE MODEL. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

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.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Lukinskiene, Linalukinsk@yahoo.com
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairDi, Yuan Pupdi@eoh.pitt.eduPETERDI
Committee MemberPitt, Brucebpitt@eoh.pitt.eduBRUCEP
Committee MemberSteele, ChadChad.Steele@chp.edu
Date: 8 July 2005
Date Type: Completion
Defense Date: 10 June 2005
Approval Date: 8 July 2005
Submission Date: 6 June 2005
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Environmental and Occupational Health
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: transgenic mice; pseudomonas aeruginosa; CFU; proimflammatory cytokines
Other ID: http://etd.library.pitt.edu/ETD/available/etd-06062005-124641/, etd-06062005-124641
Date Deposited: 10 Nov 2011 19:46
Last Modified: 15 Nov 2016 13:44
URI: http://d-scholarship.pitt.edu/id/eprint/8020

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