Early tissue transglutaminase-mediated response underlies K562(S)-cell gliadin-dependent agglutination

Marco Silano, Olimpia Vincentini, Alessandro Luciani, Cristina Felli, Sergio Caserta, Speranza Esposito, Valeria Rachela Villella, Massimo Pettoello-Mantovani, Stefano Guido, Luigi Maiuri

Research output: Contribution to journalArticlepeer-review

Abstract

Intoduction: K562(S) agglutination has been used as a rapid and economic tool for the in vitro screening of the toxicity of cereal fractions and prolamins in celiac disease (CD). A strict correlation has been reported between the toxicity of cereals and cereal fractions for celiac patients and their ability to agglutinate K562(S) cells. Whether this specificity of K562(S)-cell agglutination is caused by the activation of the same pathogenic events triggered by toxic cereal fractions in CD intestine or simply represents a bystander event of gluten toxicity is, however, unknown. Methods: K562(S) cells were incubated in vitro with the peptic-tryptic digest of wheat gliadin. Results: The agglutination of K562(S) cells by wheat gliadin peptides is orchestrated by a cascade of very early events occurring at the K562(S)-cell surface similar to those occurring at the intestinal epithelial surface. They involve a rapid increase in intracellular calcium levels that activate tissue transglutaminase (TG2), leading to a rapid actin reorganization that is pivotal in driving cell agglutination. These specific effects of toxic cereals are phenocopied by the gliadin-derived peptide p31-43, which orchestrates the activation of innate response to gliadin in CD. Discussion: Our study provides the rationale for the extensive use of K562(S)-cell agglutination as a valuable tool for screening cereal toxicity.

Original languageEnglish
Pages (from-to)532-538
Number of pages7
JournalPediatric Research
Volume71
Issue number5
DOIs
Publication statusPublished - May 2012

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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