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Comprehensive metabolomic analysis of peanut-induced anaphylaxis in a murine model

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Abstract

Acute anaphylaxis caused by food allergy is a potentially life-threatening allergic reaction that results in thousands of hospitalizations in North America every year. There are currently no effective means of treatment for anaphylaxis beyond the administration of epinephrine which is only given after a reaction has already started. Furthermore, knowledge regarding the underlying physico-chemical basis of anaphylaxis is largely incomplete. Arguably, the study of anaphylaxis by comprehensive metabolomics offers a unique opportunity to study this phenomenon due to its ability to provide a snap-shot of the chemical state of a subject experiencing anaphylaxis encompassing both endogenous and exogenous factors including dietary and environmental effects. In this study, we sought to apply a comprehensive metabolomics approach using liquid chromatography–mass spectrometry to a murine model of peanut-induced anaphylaxis. The results of this study revealed that the metabolomic profiles of mice experiencing peanut-induced anaphylaxis followed a distinct pattern that mirrors the time-stage of anaphylaxis being experienced. Direct comparison of anaphylactic mice to time-matched control mice showed that the metabolomic profiles changed considerably as the anaphylactic reaction progressed. This comparison also revealed changes in both known biomarkers of anaphylaxis such as histamine and methylhistamine as well as a suite of metabolites chemically similar to known anaphylaxis mediators but whose biological functions are not well understood. These metabolites include a number of phospholipids such as a variety of phosphatidylcholines and lyso-phosphatidylcholines that may be of interest for further investigation regarding their potential as anaphylaxis mediators or chemical precursors to mediators.

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Abbreviations

CT:

Cholera toxin

GC–MS:

Gas chromatography–mass spectometry

i.p.:

Intraperitoneal

LC–ESI-TOF-MS:

Liquid chromatography–electrospray ionization-time-of-flight-mass spectrometry

OPLS-DA:

Orthogonal partial least squares-discriminate analysis

PIA:

Peanut-induced anaphylaxis

PAF:

Platelet activating factor

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Acknowledgments

This work was carried out with the support and funding of Anaphylaxis Canada and the National Science and Engineering Research Council of Canada. Technical assistance was provided by Tina Walker, Susanna Goncharova, and Leen Naji.

Conflict of interest

The authors declare no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Chemistry and Chemical Biology, McMaster University, A.N. Bourns Science Building-156, 1280 Main St. W., Hamilton, ON, L8S 4M1, Canada

    Kenneth R. Chalcraft & Brian E. McCarry

  2. Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre (MIRC), McMaster University, Hamilton, ON, Canada

    Joshua Kong & Manel Jordana

  3. Department of Medicine, McMaster University, Hamilton, ON, Canada

    Susan Waserman

Authors
  1. Kenneth R. Chalcraft
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  2. Joshua Kong
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  3. Susan Waserman
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  4. Manel Jordana
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  5. Brian E. McCarry
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Corresponding author

Correspondence to Kenneth R. Chalcraft.

Additional information

This work is dedicated to the memory of Brian E. McCarry. Chalcraft and Kong contributed equally to this work.

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Chalcraft, K.R., Kong, J., Waserman, S. et al. Comprehensive metabolomic analysis of peanut-induced anaphylaxis in a murine model. Metabolomics 10, 452–460 (2014). https://doi.org/10.1007/s11306-013-0589-7

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  • DOI: https://doi.org/10.1007/s11306-013-0589-7

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