title: T lymphocytes possess the machinery for 5-HT synthesis, storage, degradation and release.
abstract: OBJECTIVE
  Although activated T lymphocytes express tryptophan hydroxylase 1 and produce 5-HT, the metabolic fate and cellular handling of this 5-HT is unclear. Here, we investigated key proteins in T cells linked to 5-HT metabolism and storage and compare differences in 5-HT synthesis and metabolism between T-cell subsets.
  
  
  METHODS
  We cultured human Jurkat T cells and mouse splenic CD3(+) , CD4(+) and CD8(+) T cells with or without T-cell activators (phorbol ester/ionomycin, concavalin A or plate-bound anti-CD3 antibody). Subsequently, we measured mRNA and/or protein for monoamine oxidase A and B, vesicular monoamine transporter 1 and 2, N-acetyl transferase and tryptophan hydroxylase 1. In addition, we measured the release of exogenously loaded [(3) H]5-HT and endogenously synthesized 5-HT from CD4(+) and CD8(+) T-cell subsets.
  
  
  RESULTS
  Human and mouse T cells selectively express monoamine oxidase A. Following T-cell activation, mRNA levels of MAO-A increase robustly in parallel with tryptophan hydroxylase 1. Concomitant with these changes, T cells increase the expression of the type 1 vesicular monoamine transporter. Raised intracellular [Ca(2+) ] rapidly releases preloaded [(3) H]5-HT from CD4(+) and CD8(+) T cells indicating that these cells have the capacity for the storage and regulated secretion of 5-HT. Notably, both the expression of tryptophan hydroxylase 1 and monoamine oxidase A, and 5-HT production are significantly greater in CD8(+) compared with CD4(+) T cells.
  
  
  CONCLUSIONS
  These data reveal coordinated changes in 5-HT production, metabolism and storage that may optimize 5-HT secretion from the CD8(+) T cell subset in response to activation stimuli.
authors: Department of Pharmacology and Physiology, Georgetown University, Washington, DC, USA.
authors: Y
authors: Y
authors: Chen
authors: M
authors: M
authors: Leon-Ponte
authors: S C
authors: SC
authors: Pingle
authors: P J
authors: PJ
authors: O'Connell
authors: G P
authors: GP
authors: Ahern
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism; D016716:PC12 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D012701:Serotonin; D008995:Monoamine Oxidase
keywords: 5-HT; monoamine oxidase; vesicular monoamine transporter