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

23 Scopus citations

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 (US)
Article numberA1323
JournalPloS one
Volume10
Issue number9
DOIs
StatePublished - Sep 17 2015

ASJC Scopus subject areas

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

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    Lammers, K. M., Chieppa, M., Liu, L., Liu, S., Omatsu, T., Janka-Junttila, M., Casolaro, V., Reinecker, H. C., Parent, C. A., & 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