Eosinophil-mediated signalling attenuates inflammatory responses in experimental colitis

Joanne C. Masterson, Eóin N. McNamee, Sophie A. Fillon, Lindsay Hosford, Rachel Harris, Shahan D. Fernando, Paul Jedlicka, Ryo Iwamoto, Elizabeth Jacobsen, Cheryl Protheroe, Holger K. Eltzschig, Sean P. Colgan, Makoto Arita, James J. Lee, Glenn T. Furuta

Research output: Contribution to journalArticle

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Abstract

Objective: Eosinophils reside in the colonic mucosa and increase significantly during disease. Although a number of studies have suggested that eosinophils contribute to the pathogenesis of GI inflammation, the expanding scope of eosinophil-mediated activities indicate that they also regulate local immune responses and modulate tissue inflammation. We sought to define the impact of eosinophils that respond to acute phases of colitis in mice. Design: Acute colitis was induced in mice by administration of dextran sulfate sodium, 2,4,6-trinitrobenzenesulfonic acid or oxazolone to C57BL/6J (control) or eosinophil deficient (PHIL) mice. Eosinophils were also depleted from mice using antibodies against interleukin (IL)-5 or by grafting bone marrow from PHIL mice into control mice. Colon tissues were collected and analysed by immunohistochemistry, flow cytometry and reverse transcription PCR; lipids were analysed by mass spectroscopy. Results: Eosinophil-deficient mice developed significantly more severe colitis, and their colon tissues contained a greater number of neutrophils, than controls. This compensatory increase in neutrophils was accompanied by increased levels of the chemokines CXCL1 and CXCL2, which attract neutrophils. Lipidomic analyses of colonic tissue from eosinophil-deficient mice identified a deficiency in the docosahexaenoic acidderived anti-inflammatory mediator 10, 17-dihydroxydocosahexaenoic acid (diHDoHE), namely protectin D1 (PD1). Administration of an exogenous PD1-isomer (10S, 17S-DiHDoHE) reduced the severity of colitis in eosinophil-deficient mice. The PD1-isomer also attenuated neutrophil infiltration and reduced levels of tumour necrosis factor-α, IL-1β, IL-6 and inducible NO-synthase in colons of mice. Finally, in vitro assays identified a direct inhibitory effect of PD1-isomer on neutrophil transepithelial migration. Conclusions: Eosinophils exert a protective effect in acute mouse colitis, via production of anti-inflammatory lipid mediators.

Original languageEnglish
Pages (from-to)1236-1247
Number of pages12
JournalGut
Volume64
Issue number8
DOIs
Publication statusPublished - 2015 Aug 1
Externally publishedYes

Fingerprint

Colitis
Eosinophils
Neutrophils
Colon
Chemokine CXCL1
Anti-Inflammatory Agents
Trinitrobenzenesulfonic Acid
Oxazolone
Chemokine CXCL2
Inflammation
Transendothelial and Transepithelial Migration
Lipids
Dextran Sulfate
Neutrophil Infiltration
Interleukin-5
Bone Marrow Transplantation
Interleukin-1
Nitric Oxide Synthase
Reverse Transcription
Interleukin-6

ASJC Scopus subject areas

  • Gastroenterology
  • Medicine(all)

Cite this

Masterson, J. C., McNamee, E. N., Fillon, S. A., Hosford, L., Harris, R., Fernando, S. D., ... Furuta, G. T. (2015). Eosinophil-mediated signalling attenuates inflammatory responses in experimental colitis. Gut, 64(8), 1236-1247. https://doi.org/10.1136/gutjnl-2014-306998

Eosinophil-mediated signalling attenuates inflammatory responses in experimental colitis. / Masterson, Joanne C.; McNamee, Eóin N.; Fillon, Sophie A.; Hosford, Lindsay; Harris, Rachel; Fernando, Shahan D.; Jedlicka, Paul; Iwamoto, Ryo; Jacobsen, Elizabeth; Protheroe, Cheryl; Eltzschig, Holger K.; Colgan, Sean P.; Arita, Makoto; Lee, James J.; Furuta, Glenn T.

In: Gut, Vol. 64, No. 8, 01.08.2015, p. 1236-1247.

Research output: Contribution to journalArticle

Masterson, JC, McNamee, EN, Fillon, SA, Hosford, L, Harris, R, Fernando, SD, Jedlicka, P, Iwamoto, R, Jacobsen, E, Protheroe, C, Eltzschig, HK, Colgan, SP, Arita, M, Lee, JJ & Furuta, GT 2015, 'Eosinophil-mediated signalling attenuates inflammatory responses in experimental colitis', Gut, vol. 64, no. 8, pp. 1236-1247. https://doi.org/10.1136/gutjnl-2014-306998
Masterson JC, McNamee EN, Fillon SA, Hosford L, Harris R, Fernando SD et al. Eosinophil-mediated signalling attenuates inflammatory responses in experimental colitis. Gut. 2015 Aug 1;64(8):1236-1247. https://doi.org/10.1136/gutjnl-2014-306998
Masterson, Joanne C. ; McNamee, Eóin N. ; Fillon, Sophie A. ; Hosford, Lindsay ; Harris, Rachel ; Fernando, Shahan D. ; Jedlicka, Paul ; Iwamoto, Ryo ; Jacobsen, Elizabeth ; Protheroe, Cheryl ; Eltzschig, Holger K. ; Colgan, Sean P. ; Arita, Makoto ; Lee, James J. ; Furuta, Glenn T. / Eosinophil-mediated signalling attenuates inflammatory responses in experimental colitis. In: Gut. 2015 ; Vol. 64, No. 8. pp. 1236-1247.
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AU - Harris, Rachel

AU - Fernando, Shahan D.

AU - Jedlicka, Paul

AU - Iwamoto, Ryo

AU - Jacobsen, Elizabeth

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AU - Eltzschig, Holger K.

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