Secreted Metabolome of Human Macrophages Exposed to Methamphetamine

Katarzyna Pawlak, Katarzyna Lech, Akou Vei, Sydney Burch, Sarah Zieschang, Spencer Jaquet, Fang Yu, Emma Harwood, Brenda Morsey, Howard S. Fox, Pawel Ciborowski

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Abstract

Macrophages comprise a major component of the human innate immune system that is involved in maintaining homeostasis and responding to infections or other insults. Besides cytokines and chemokines, macrophages presumably influence the surrounding environment by secreting various types of metabolites. Characterization of secreted metabolites under normal and pathological conditions is critical for understanding the complex innate immune system. To investigate the secreted metabolome, we developed a novel workflow consisting of one Reverse Phase (RP) C18 column linked in tandem with a Cogent cholesterol-modified RP C18. This system was used to compare the secreted metabolomes of human monocyte-derived macrophages (hMDM) under normal conditions to those exposed to methamphetamine (Meth). This new experimental approach allowed us to measure 92 metabolites, identify 11 of them as differentially expressed, separate and identify three hydroxymethamphetamine (OHMA) isomers, and identify a new, yet unknown metabolite with a m/z of 192. This study is the first of its kind to address the secreted metabolomic response of hMDM to an insult by Meth. Besides the discovery of novel metabolites secreted by macrophages, we provide a novel methodology to investigate metabolomic profiling.

Original languageEnglish (US)
Pages (from-to)9190-9197
Number of pages8
JournalAnalytical chemistry
Volume91
Issue number14
DOIs
StatePublished - Jun 20 2019

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ASJC Scopus subject areas

  • Analytical Chemistry

Cite this

Pawlak, K., Lech, K., Vei, A., Burch, S., Zieschang, S., Jaquet, S., Yu, F., Harwood, E., Morsey, B., Fox, H. S., & Ciborowski, P. (2019). Secreted Metabolome of Human Macrophages Exposed to Methamphetamine. Analytical chemistry, 91(14), 9190-9197. https://doi.org/10.1021/acs.analchem.9b01952