Gliadin induces neutrophil migration via engagement of the formyl peptide receptor, FPR1

Karen M. Lammers, Marcello Chieppa, Lunhua Liu, Song Liu, Tatsushi Omatsu, Mirkka Janka-Junttila, Vincenzo Casolaro, Hans Christian Reinecker, Carole A. Parent, Alessio Fasano

Research output: Contribution to journalArticle

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Abstract

Background Gliadin, the immunogenic component within gluten and trigger of celiac disease, is known to induce the production of Interleukin-8, a potent neutrophil-Activating and chemoattractant chemokine.We sought to study the involvement of neutrophils in the early immunological changes following gliadin exposure. Methods Utilizing immunofluorescence microscopy and flow cytometry, the redistribution of major tight junction protein, Zonula occludens (ZO)-1, and neutrophil recruitment were assessed in duodenal tissues of gliadin-gavaged C57BL/6 wild-Type and Lys-GFP reporter mice, respectively. Intravital microscopy with Lys-GFP mice allowed monitoring of neutrophil recruitment in response to luminal gliadin exposure in real time. In vitro chemotaxis assays were used to study murine and human neutrophil chemotaxis to gliadin, synthetic alpha-gliadin peptides and the neutrophil chemoattractant, fMet-Leu-Phe, in the presence or absence of a specific inhibitor of the fMet-Leu-Phe receptor-1 (FPR1), cyclosporine H. An irrelevant protein, zein, served as a control. Results Redistribution of ZO-1 and an influx of CD11b+Lys6G+ cells in the lamina propria of the small intestine were observed upon oral gavage of gliadin. In vivo intravital microscopy revealed a slowing down of GFP+ cells within the vessels and influx in the mucosal tissue within 2 hours after challenge. In vitro chemotaxis assays showed that gliadin strongly induced neutrophil migration, similar to fMet-Leu-Phe.We identified thirteen synthetic gliadin peptide motifs that induced cell migration. Blocking of FPR1 completely abrogated the fMet-Leu-Phe-, gliadin- and synthetic peptide-induced migration. Conclusions Gliadin possesses neutrophil chemoattractant properties similar to the classical neutrophil chemoattractant, fMet-Leu-Phe, and likewise uses FPR1 in the process.

Original languageEnglish
Article numberA1323
JournalPLoS One
Volume10
Issue number9
DOIs
Publication statusPublished - Sep 17 2015

Fingerprint

Formyl Peptide Receptor
Gliadin
gliadin
neutrophils
Neutrophils
receptors
N-Formylmethionine Leucyl-Phenylalanine
chemoattractants
Chemotactic Factors
tight junctions
chemotaxis
Chemotaxis
Neutrophil Infiltration
Tight Junctions
Peptides
Assays
microscopy
mice
Mucous Membrane
peptide receptors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Lammers, K. M., Chieppa, M., Liu, L., Liu, S., Omatsu, T., Janka-Junttila, M., ... Fasano, A. (2015). Gliadin induces neutrophil migration via engagement of the formyl peptide receptor, FPR1. PLoS One, 10(9), [A1323]. https://doi.org/10.1371/journal.pone.0138338

Gliadin induces neutrophil migration via engagement of the formyl peptide receptor, FPR1. / Lammers, Karen M.; Chieppa, Marcello; Liu, Lunhua; Liu, Song; Omatsu, Tatsushi; Janka-Junttila, Mirkka; Casolaro, Vincenzo; Reinecker, Hans Christian; Parent, Carole A.; Fasano, Alessio.

In: PLoS One, Vol. 10, No. 9, A1323, 17.09.2015.

Research output: Contribution to journalArticle

Lammers, KM, Chieppa, M, Liu, L, Liu, S, Omatsu, T, Janka-Junttila, M, Casolaro, V, Reinecker, HC, Parent, CA & Fasano, A 2015, 'Gliadin induces neutrophil migration via engagement of the formyl peptide receptor, FPR1', PLoS One, vol. 10, no. 9, A1323. https://doi.org/10.1371/journal.pone.0138338
Lammers KM, Chieppa M, Liu L, Liu S, Omatsu T, Janka-Junttila M et al. Gliadin induces neutrophil migration via engagement of the formyl peptide receptor, FPR1. PLoS One. 2015 Sep 17;10(9). A1323. https://doi.org/10.1371/journal.pone.0138338
Lammers, Karen M. ; Chieppa, Marcello ; Liu, Lunhua ; Liu, Song ; Omatsu, Tatsushi ; Janka-Junttila, Mirkka ; Casolaro, Vincenzo ; Reinecker, Hans Christian ; Parent, Carole A. ; Fasano, Alessio. / Gliadin induces neutrophil migration via engagement of the formyl peptide receptor, FPR1. In: PLoS One. 2015 ; Vol. 10, No. 9.
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abstract = "Background Gliadin, the immunogenic component within gluten and trigger of celiac disease, is known to induce the production of Interleukin-8, a potent neutrophil-Activating and chemoattractant chemokine.We sought to study the involvement of neutrophils in the early immunological changes following gliadin exposure. Methods Utilizing immunofluorescence microscopy and flow cytometry, the redistribution of major tight junction protein, Zonula occludens (ZO)-1, and neutrophil recruitment were assessed in duodenal tissues of gliadin-gavaged C57BL/6 wild-Type and Lys-GFP reporter mice, respectively. Intravital microscopy with Lys-GFP mice allowed monitoring of neutrophil recruitment in response to luminal gliadin exposure in real time. In vitro chemotaxis assays were used to study murine and human neutrophil chemotaxis to gliadin, synthetic alpha-gliadin peptides and the neutrophil chemoattractant, fMet-Leu-Phe, in the presence or absence of a specific inhibitor of the fMet-Leu-Phe receptor-1 (FPR1), cyclosporine H. An irrelevant protein, zein, served as a control. Results Redistribution of ZO-1 and an influx of CD11b+Lys6G+ cells in the lamina propria of the small intestine were observed upon oral gavage of gliadin. In vivo intravital microscopy revealed a slowing down of GFP+ cells within the vessels and influx in the mucosal tissue within 2 hours after challenge. In vitro chemotaxis assays showed that gliadin strongly induced neutrophil migration, similar to fMet-Leu-Phe.We identified thirteen synthetic gliadin peptide motifs that induced cell migration. Blocking of FPR1 completely abrogated the fMet-Leu-Phe-, gliadin- and synthetic peptide-induced migration. Conclusions Gliadin possesses neutrophil chemoattractant properties similar to the classical neutrophil chemoattractant, fMet-Leu-Phe, and likewise uses FPR1 in the process.",
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AU - Janka-Junttila, Mirkka

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