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

Lipidomic profiling in Crohn’s disease: abnormalities in phosphatidylinositols, with preservation of ceramide, phosphatidylcholine and phosphatidylserine composition
Lipidomic profiling in Crohn’s disease: abnormalities in phosphatidylinositols, with preservation of ceramide, phosphatidylcholine and phosphatidylserine composition
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.

1357-2725
1839-1846
Sewell, G.W.
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Hannun, Y.A.
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Han, X.
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Koster, G.
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Bielawski, J.
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Goss, V.
b51e044d-48fa-414c-bea9-a58d2b15eeff
Smith, P.J.
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Rahman, F.Z.
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Vega, R.
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Bloom, S.L.
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Walker, A.P.
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Postle, Anthony D.
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Segal, A.W.
88f2ec09-54d0-48ba-9686-327ec9f75d88
Sewell, G.W.
1c06e2d7-20dd-443a-be99-9b8a9bbb45d2
Hannun, Y.A.
7cdf56cf-a45b-4ff3-b986-1865886b6ddd
Han, X.
0b4e4187-1116-4090-94f6-74ddaf02fb6d
Koster, G.
c757aa1a-f456-4159-9332-a57caa1c35a7
Bielawski, J.
6e207de8-0fb4-4373-b3f0-d26a4ab28025
Goss, V.
b51e044d-48fa-414c-bea9-a58d2b15eeff
Smith, P.J.
155b0a58-f31a-4a5c-b158-aa998aa19575
Rahman, F.Z.
38766d8d-dd5e-4fdb-9b1f-1851b99711ef
Vega, R.
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Bloom, S.L.
582f53ca-4dd9-4ed5-af1f-2fdb9b70e69c
Walker, A.P.
1b16cd22-afb9-47ef-a7af-a49b3f686f4c
Postle, Anthony D.
0fa17988-b4a0-4cdc-819a-9ae15c5dad66
Segal, A.W.
88f2ec09-54d0-48ba-9686-327ec9f75d88

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, Anthony D. and 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 & Cell Biology, 44 (11), 1839-1846. (doi:10.1016/j.biocel.2012.06.016).

Record type: Article

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.

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Published date: November 2012
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 353211
URI: http://eprints.soton.ac.uk/id/eprint/353211
ISSN: 1357-2725
PURE UUID: ee42f131-34f6-4b5c-9613-908c269849ca
ORCID for Anthony D. Postle: ORCID iD orcid.org/0000-0001-7361-0756

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Date deposited: 03 Jun 2013 13:21
Last modified: 19 Nov 2019 02:04

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Contributors

Author: G.W. Sewell
Author: Y.A. Hannun
Author: X. Han
Author: G. Koster
Author: J. Bielawski
Author: V. Goss
Author: P.J. Smith
Author: F.Z. Rahman
Author: R. Vega
Author: S.L. Bloom
Author: A.P. Walker
Author: A.W. Segal

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