• Login
    View Item 
    •   UTSW DSpace Home
    • UT Southwestern Electronic Theses and Dissertations
    • UT Southwestern Electronic Theses and Dissertations
    • View Item
    •   UTSW DSpace Home
    • UT Southwestern Electronic Theses and Dissertations
    • UT Southwestern Electronic Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Constitutive Overexpression of Acyloxyacyl Hydrolase in Mus Musculus

    Thumbnail
    View/Open
    Dissertation available now (1.453Mb)
    Date
    2009-01-14
    Author
    Ojogun, Noredia I.
    Metadata
    Show full item record
    Abstract
    Acyloxyacyl hydrolase (AOAH) is a highly conserved host lipase that selectively removes the secondary acyl chains from lipid A, the bioactive center of Gram negative bacterial lipopolysaccharide (LPS). Deacylated LPS has a marked reduction in bioactivity and antagonizes the LPS signaling pathway. Thus, AOAH deacylation of LPS may represent a mechanism by which animals control responses to Gram-negative bacteria. Prior to the experiments described in this study, mice deficient in AOAH were found to be susceptible to the long-term effects of LPS. Aoah-/- mice developed long-lasting hepatomegaly, exaggerated antibody responses, and prolonged immunosuppression in response to small doses of LPS. In the studies described here, AOAH was overexpressed in mice by using CD68 promoter sequences which have been shown by others to drive transgene expression in macrophages. CD68p-AOAH transgenic mice had constitutive overexpression of AOAH in macrophages, dendritic cells and tissues rich in these cells (liver, spleen and lung). They also secreted the enzyme into blood and deacylated LPS at a faster rate both in vitro and in vivo. Importantly, constitutive overexpression of AOAH did not interfere with the initial pro-inflammatory responses to LPS, in keeping with prior observations that AOAH-mediated inactivation of LPS occurs over several hours and does not moderate acute reactions to LPS in vivo. The protective role of constitutive AOAH overexpression was determined by two test systems. First, after an intraperitoneal dose of LPS, CD68p-AOAH transgenic mice returned to their pre-challenge weights more rapidly than did the wildtype mice. Secondly, CD68p-AOAH transgenic mice were less susceptible to LPS and Gram-negative bacteria induced hepatosplenomegaly. These results suggest that overexpression of AOAH in macrophages could accelerate recovery from Gram-negative bacterial infections in animals, including humans.
    URI
    http://hdl.handle.net/2152.5/383
    Collections
    • UT Southwestern Electronic Theses and Dissertations

    UT Southwestern Health Sciences Digital Library and Learning Center | 5323 Harry Hines Boulevard, Dallas, Texas 75390-9049
    Telephone 214-648-2001 | Email
    Library Home | UT Southwestern Home
    DSpace software copyright © 2002-2016  DuraSpace
    Contact Us | Send Feedback
    TDL
    Theme by 
    Atmire NV
     

     

    Browse

    All of DSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    Login

    UT Southwestern Health Sciences Digital Library and Learning Center | 5323 Harry Hines Boulevard, Dallas, Texas 75390-9049
    Telephone 214-648-2001 | Email
    Library Home | UT Southwestern Home
    DSpace software copyright © 2002-2016  DuraSpace
    Contact Us | Send Feedback
    TDL
    Theme by 
    Atmire NV