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Thomas Poulsen

Proteomic analysis of lipopolysaccharide activated human monocytes

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  • Mads Lausen, Laboratory for Medical Mass Spectrometry. Department of Health Science and Technology, Aalborg University Fredrik Bajers Vej 3b, Aalborg Ø, 9220 Aalborg, Denmark.
  • ,
  • Thomas B G Poulsen
  • Gunna Christiansen
  • Kenneth Kastaniegaard, Laboratory for Medical Mass Spectrometry. Department of Health Science and Technology, Aalborg University Fredrik Bajers Vej 3b, Aalborg Ø, 9220 Aalborg, Denmark.
  • ,
  • Allan Stensballe
  • Svend Birkelund, Laboratory for Medical Mass Spectrometry. Department of Health Science and Technology, Aalborg University Fredrik Bajers Vej 3b, Aalborg Ø, 9220 Aalborg, Denmark. Electronic address: sbirkelund@hst.aau.dk.

Monocytes are key mediators of innate immunity and comprise an important cellular defence against invading pathogens. However, exaggerated or dysregulated monocyte activation can lead to severe immune-mediated pathology such as sepsis or chronic inflammatory diseases. Thus, detailed insight into the molecular mechanisms of monocyte activation is essential to understand monocyte-driven inflammatory pathologies. We therefore investigated the global protein changes in human monocytes during lipopolysaccharide (LPS) activation to mimic bacterial activation. Purified human monocytes were stimulated with LPS for 17 h and analyzed by state-of-the-art liquid chromatography tandem mass spectrometry (LC-MS/MS). The label-free quantitative proteome analysis identified 2746 quantifiable proteins of which 101 had a statistically significantly different abundance between LPS-stimulated cells and unstimulated controls. Additionally, 143 proteins were exclusively identified in either LPS stimulated cells or unstimulated controls. Functional annotation clustering demonstrated that LPS, most significantly, regulates proteasomal- and lysosomal proteins but in opposite directions. Thus, seven proteasome subunits were upregulated by LPS while 11 lysosomal proteins were downregulated. Both systems are critically involved in processing of proteins for antigen-presentation and together with LPS-induced regulation of CD74 and tapasin, our data suggest that LPS can skew monocytic antigen-presentation towards MHC class I rather than MHC class II. In summary, this study provides a sensitive high throughput protein analysis of LPS-induced monocyte activation and identifies several LPS-regulated proteins not previously described in the literature which can be used as a source for future studies.

Original languageEnglish
JournalMolecular Immunology
Volume103
Pages (from-to)257-269
Number of pages13
ISSN0161-5890
DOIs
Publication statusPublished - Nov 2018

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