Lipid and lipid mediator profiling of human synovial fluid in rheumatoid arthritis patients by means of LC-MS/MS - PubMed (original) (raw)

Lipid and lipid mediator profiling of human synovial fluid in rheumatoid arthritis patients by means of LC-MS/MS

Martin Giera et al. Biochim Biophys Acta. 2012 Nov.

Abstract

Human synovial fluid (SF) provides nutrition and lubrication to the articular cartilage. Particularly in arthritic diseases, SF is extensively accumulating in the synovial junction. During the last decade lipids have attracted considerable attention as their role in the development and resolution of diseases became increasingly recognized. Here, we describe a capillary LC-MS/MS screening platform that was used for the untargeted screening of lipids present in human SF of rheumatoid arthritis (RA) patients. Using this platform we give a detailed overview of the lipids and lipid-derived mediators present in the SF of RA patients. Almost 70 different lipid components from distinct lipid classes were identified and quantification was achieved for the lysophosphatidylcholine and phosphatidylcholine species. In addition, we describe a targeted LC-MS/MS lipid mediator metabolomics strategy for the detection, identification and quantification of maresin 1, lipoxin A(4) and resolvin D5 in SF from RA patients. Additionally, we present the identification of 5S,12S-diHETE as a major marker of lipoxygenase pathway interactions in the investigated SF samples. These results are the first to provide a comprehensive approach to the identification and profiling of lipids and lipid mediators present in SF and to describe the presence of key anti-inflammatory and pro-resolving lipid mediators identified in SF from RA patients.

Copyright © 2012 Elsevier B.V. All rights reserved.

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Figures

Figure 1

Figure 1

Base Peak Intensity chromatograms (BPI) of the ESI+ mode (above) and the ESI-mode (below), the abbreviations mark the elution windows of the different lipid classes, assignments are given in the ESI+, ESI- or both modes according to table 1

Figure 2

Figure 2

comparison of different MS2 extracted ion chromatograms (EIC), lower right corner mass spectrometric identification of PI(18:0/20:4) [46]

Figure 3

Figure 3

MS/MS spectra of SM(34:1) in the positive and negative ESI mode

Figure 4

Figure 4

Extracted ion chromatogram (ESI-) of the ion traces m/z 327.2, 343.3, 301.2, 317.2, 319.2 and 335.3 referring to FA 22:6, FA 20:5, their respective hydroxylated species and 5S,12S-diHETE in the RA pool sample. The upper left corner shows the obtained MS/MS spectrum for the precursor _m/_z 335 at 1.6 min. The upper right corner shows 5S,12S-diHETE and its preferred fragmentation yielding m/z 195.

Figure 5

Figure 5

Identification of MaR1 in human synovial fluid, upper left corner selected reaction monitoring chromatograms of the transition m/z 359→221, black – unspiked sample, red - co-injection of a synthetic MaR1 standard (100 pg on column spike level), upper right corner – MS/MS spectrum of MaR1, lower right corner - MS3 spectrum of the characteristic MaR1 fragment m/z 221 corresponding to the sample, lower left corner MS3 spectrum of synthetic MaR1 (m/z 221) – standard sample (10 pg on column).

Figure 6

Figure 6

Lipid mediator amounts identified and quantified in five different human SF samples. Absolute amounts in pg on column are given. Error bars show one standard deviation (n=5). For the individual values see supplementary material S5.

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References

    1. Hui AY, McCarty WJ, Masuda K, Firestein GS, Sah RL. A systems biology approach to synovial joint lubrication in health, injury, and disease, Wiley Interdiscip. Rev. Syst. Biol. Med. 2012;4:15–37. - PMC - PubMed
    1. McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat. Rev. Immunol. 2007;7:429–442. - PubMed
    1. Bird HA, Ring EF. Therapeutic value of arthroscopy. Ann. Rheum. Dis. 1978;37:78–79. - PMC - PubMed
    1. Serhan CN. Novel lipid mediators and resolution mechanisms in acute inflammation: to resolve or not? Am. J .Pathol. 2010;177:1576–1591. - PMC - PubMed
    1. Chen M, Lam BK, Kanaoka Y, Nigrovic PA, Audoly LP, Austen KF, Lee DM. Neutrophil-derived leukotriene B4 is required for inflammatory arthritis. J. Exp. Med. 2006;203:837–842. - PMC - PubMed

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