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

Simple item page
dc.access.optionOpen Access
dc.contributor.authorOgburn, David
dc.contributor.authorBhalla, Sophia
dc.contributor.authorLeffler, Nan
dc.contributor.authorMohan, Arjun
dc.contributor.authorMalur, Anagha
dc.contributor.authorMalur, Achut G.
dc.contributor.authorMcPeek, Matthew
dc.contributor.authorBarna, Barbara P.
dc.contributor.authorThomassen, Mary Jane
dc.date.accessioned2022-01-31T16:24:39Z
dc.date.available2022-01-31T16:24:39Z
dc.date.issued2021-10-13
dc.description.abstractSarcoidosis 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.
dc.description.sponsorshipECU Open Access Publishing Support Funden_US
dc.identifier.doi10.3390/ijms222011019
dc.identifier.urihttp://hdl.handle.net/10342/9575
dc.publisherMDPI
dc.relation.urihttps://doi.org/10.3390/ijms222011019en_US
dc.subjectsarcoidosis
dc.subjectMMP12
dc.subjectPPAR?
dc.subjectMWCNT
dc.subjectgranuloma
dc.subjectinflammation
dc.titleThe M2a macrophage phenotype accompanies pulmonary granuloma resolution in Mmp12 knock-out mice instilled with multiwall carbon nanotubes
dc.typeArticle
ecu.journal.issue20en_US
ecu.journal.nameInternational Journal of Molecular Sciencesen_US
ecu.journal.pages16en_US
ecu.journal.volume22en_US

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Thomassen2021.pdf
Size:
5.48 MB
Format:
Adobe Portable Document Format
Download

Collections

2021-2022 Open Access Publishing Fund
Internal Medicine