Lipidomic profiling in Crohn's disease: Abnormalities in phosphatidylinositols, with preservation of ceramide, phosphatidylcholine and phosphatidylserine composition

Gavin W. Sewell, Yusuf A. Hannun, Xianlin Han, Grielof Koster, Jacek Bielawski, Victoria Goss, Philip J. Smith, Farooq Z. Rahman, Roser Vega, Stuart L. Bloom, Ann P. Walker, Anthony D. Postle, Anthony W. Segal

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Crohn's disease is a chronic inflammatory condition largely affecting the terminal ileum and large bowel. A contributing cause is the failure of an adequate acute inflammatory response as a result of impaired secretion of pro-inflammatory cytokines by macrophages. This defective secretion arises from aberrant vesicle trafficking, misdirecting the cytokines to lysosomal degradation. Aberrant intestinal permeability is also well-established in Crohn's disease. Both the disordered vesicle trafficking and increased bowel permeability could result from abnormal lipid composition. We thus measured the sphingo- and phospholipid composition of macrophages, using mass spectrometry and stable isotope labelling approaches. Stimulation of macrophages with heat-killed Escherichia coli resulted in three main changes; a significant reduction in the amount of individual ceramide species, an altered composition of phosphatidylcholine, and an increased rate of phosphatidylcholine synthesis in macrophages. These changes were observed in macrophages from both healthy control individuals and patients with Crohn's disease. The only difference detected between control and Crohn's disease macrophages was a reduced proportion of newly-synthesised phosphatidylinositol 16:0/18:1 over a defined time period. Shotgun lipidomics analysis of macroscopically non-inflamed ileal biopsies showed a significant decrease in this same lipid species with overall preservation of sphingolipid, phospholipid and cholesterol composition.

Original languageEnglish (US)
Pages (from-to)1839-1846
Number of pages8
JournalInternational Journal of Biochemistry and Cell Biology
Volume44
Issue number11
DOIs
StatePublished - Nov 2012
Externally publishedYes

Keywords

  • Ceramide
  • Crohn's disease
  • Lipids
  • Macrophage
  • Phospholipid
  • Sphingolipid

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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  • Cite this

    Sewell, G. W., Hannun, Y. A., Han, X., Koster, G., Bielawski, J., Goss, V., Smith, P. J., Rahman, F. Z., Vega, R., Bloom, S. L., Walker, A. P., Postle, A. D., & Segal, A. W. (2012). Lipidomic profiling in Crohn's disease: Abnormalities in phosphatidylinositols, with preservation of ceramide, phosphatidylcholine and phosphatidylserine composition. International Journal of Biochemistry and Cell Biology, 44(11), 1839-1846. https://doi.org/10.1016/j.biocel.2012.06.016