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    The M2a macrophage phenotype accompanies pulmonary granuloma resolution in Mmp12 knock-out mice instilled with multiwall carbon nanotubes

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    Author
    Ogburn, David; Bhalla, Sophia; Leffler, Nan; Mohan, Arjun; Malur, Anagha; Malur, Achut G.; McPeek, Matthew; Barna, Barbara P.; Thomassen, Mary Jane
    Abstract
    Sarcoidosis is a chronic disease with unknown etiology and pathophysiology, characterized by granuloma formation. Matrix Metalloproteinase-12 (MMP12) is an elastase implicated in active granulomatous sarcoidosis. Previously, we reported that oropharyngeal instillation of multiwall carbon nanotubes (MWCNT) into C57Bl/6 mice induced sarcoid-like granulomas and upregulation of MMP12. When Mmp12 knock-out (KO) mice were instilled with MWCNT, granuloma formation occurred 10 days post-instillation but subsequently resolved at 60 days. Thus, we concluded that MMP12 was essential to granuloma persistence. The aim of the current study was to identify potential mechanisms of granuloma resolution in Mmp12KO mice. Strikingly, an M2 macrophage phenotype was present in Mmp12KO but not in C57Bl/6 mice. Between 10 and 60 days, macrophage populations in MWCNT-instilled Mmp12KO mice demonstrated an M2c to M2a phenotypic shift, with elevations in levels of IL-13, an M2 subtype-regulating factor. Furthermore, the M2 inducer, Apolipoprotein E (ApoE), and Matrix Metalloproteinase-14 (MMP14), a promoter of collagen degradation, were upregulated in 60-day MWCNT-instilled Mmp12KO mice. In conclusion, alveolar macrophages express two M2 phenotypes in Mmp12KO mice: M2c at 10 days when granulomas form, and M2a at 60 days when granulomas are resolving. Findings suggest that granuloma resolution in 60-day Mmp12KO mice requires an M2a macrophage phenotype.
    URI
    http://hdl.handle.net/10342/9575
    Subject
     sarcoidosis; MMP12; PPAR?; MWCNT; granuloma; inflammation 
    Date
    2021-10-13
    Citation:
    APA:
    Ogburn, David, & Bhalla, Sophia, & Leffler, Nan, & Mohan, Arjun, & Malur, Anagha, & Malur, Achut G., & McPeek, Matthew, & Barna, Barbara P., & Thomassen, Mary Jane. (October 2021). The M2a macrophage phenotype accompanies pulmonary granuloma resolution in Mmp12 knock-out mice instilled with multiwall carbon nanotubes. , (), - . Retrieved from http://hdl.handle.net/10342/9575

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    MLA:
    Ogburn, David, and Bhalla, Sophia, and Leffler, Nan, and Mohan, Arjun, and Malur, Anagha, and Malur, Achut G., and McPeek, Matthew, and Barna, Barbara P., and Thomassen, Mary Jane. "The M2a macrophage phenotype accompanies pulmonary granuloma resolution in Mmp12 knock-out mice instilled with multiwall carbon nanotubes". . . (), October 2021. January 31, 2023. http://hdl.handle.net/10342/9575.
    Chicago:
    Ogburn, David and Bhalla, Sophia and Leffler, Nan and Mohan, Arjun and Malur, Anagha and Malur, Achut G. and McPeek, Matthew and Barna, Barbara P. and Thomassen, Mary Jane, "The M2a macrophage phenotype accompanies pulmonary granuloma resolution in Mmp12 knock-out mice instilled with multiwall carbon nanotubes," , no. (October 2021), http://hdl.handle.net/10342/9575 (accessed January 31, 2023).
    AMA:
    Ogburn, David, Bhalla, Sophia, Leffler, Nan, Mohan, Arjun, Malur, Anagha, Malur, Achut G., McPeek, Matthew, Barna, Barbara P., Thomassen, Mary Jane. The M2a macrophage phenotype accompanies pulmonary granuloma resolution in Mmp12 knock-out mice instilled with multiwall carbon nanotubes. . October 2021; (): . http://hdl.handle.net/10342/9575. Accessed January 31, 2023.
    Collections
    • 2021-2022 Open Access Publishing Fund
    • Internal Medicine
    Publisher
    MDPI

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