Early tissue transglutaminase mediated response underlies k562(s) cells gliadin – dependent agglutination

K562(S) agglutination has been used as a rapid and economic tool for the in vitro screening of the toxicity of cereals 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. Here we demonstrate that 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 of intracellular Calcium levels that activate tissue transglutaminase 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 that orchestrates the activation of innate response to gliadin in celiac disease. Our study provides the rationale for the extensive use of K562(S) cell agglutination as a priceless tool for screening cereal toxicity.