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J Endocrinol 2017;232:R67-R81,9l-]9  9 X J  T3z ?D Z @ 2017 Society for Endocrinology*!l-]!  ! & X  x 6N  6qљYs ? ̙33ZR___PPT102.]0G+D' = @B D' = @BA?%,( < +O%,( < ++6 5 @r(  @  C ?z7   T3z ? 9   V Hypothetical pathways explaining the effects of thyroid hormone on neutrophil NAPDH oxidase activity and bacterial killing. Thyroid hormone induces neutrophil NADPH oxidase (NOX) activity, resulting in increased production of reactive oxygen species. This phenomenon is thought to be mediated via a non-genomic pathway involving binding of TH to a G-protein-coupled receptor (GPCR), which induces NAPDH oxidase activity. This effect is dependent on protein kinase C (PKC) and adequate intracellular Ca2+ levels (Mezosi et al. 2005). Intracellular thyroid hormone metabolism may also play a role in neutrophils during bacterial killing. The thyroid hormone-inactivating type 3 deiodinase (D3) is present in murine and human neutrophils (Boelen et al. 2005, 2008, van der Spek et al. 2016). Mice that lack this enzyme suffer from impaired bacterial killing (Boelen et al. 2009). D3 is located in the cytoplasm and in granules containing either myeloperoxidase (MPO) or lactoferrin (LF) (van der Spek et al. 2016). TH enters the neutrophil via transporters (MCT8 or MCT10) where it is inactivated by D3, which removes an iodine atom from the inner ring of the hormone, converting T4 to reverse (r)T3 and T3 to T2. Increased D3 activity therefore results in decreased intracellular levels of T3 together with the production of free iodide (I"). One hypothesis explaining the role of D3 in microbial killing is that the iodide produced by D3 is utilized by MPO together with hydrogen peroxidase (H2O2) to generate hypoiodite (IOH), a toxic compound that is capable of killing bacteria (Klebanoff 1967, Boelen et al. 2011). The reduction of intracellular T3 levels could theoretically also result in altered gene transcription, but no TH-responsive genes have been found in neutrophils yet. 0 l-]# + !# # # # # # S# # # # # + # + # + # + P# + /# + !# + # + m# # )# + #   & X  x 6H  0޽h ? ̙33rP> ^ 1Root EntrydO)CompObj9Ole Current User,PicturesjSummaryInformation(xPowerPoint Document(;J1DocumentSummaryInformation8