Early Tissue Transglutaminase Mediated Response Underlies K562(S) Cells Gliadin - Dependent Agglutination
Abstract
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
Autore Pugliese
Tutti gli autori
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M. Silano , O. Vincentini , A. Luciani , S. Caserta , C. Felli , S. Esposito , V.R. Villella , M. Pettoello Mantovani , S. Guido , L. Maiuri
Titolo volume/Rivista
PEDIATRIC RESEARCH
Anno di pubblicazione
2012
ISSN
0031-3998
ISBN
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