Early tissue transglutaminase-mediated response underlies K562(S)-cell gliadin-dependent agglutination.
BACKGROUND
[corrected] 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.


CONCLUSIONS
Our study provides the rationale for the extensive use of K562(S)-cell agglutination as a valuable tool for screening cereal toxicity.
Unit of Human Nutrition and Health, Istituto Superiore di Sanità, Rome, Italy. marco.silano@iss.it
Marco
M
Silano
Olimpia
O
Vincentini
Alessandro
A
Luciani
Cristina
C
Felli
Sergio
S
Caserta
Speranza
S
Esposito
Valeria Rachela
VR
Villella
Massimo
M
Pettoello-Mantovani
Stefano
S
Guido
Luigi
L
Maiuri
D002448:Cell Adhesion; D004789:Enzyme Activation; D019204:GTP-Binding Proteins; D005903:Gliadin / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000378:metabolism*
D005903:Gliadin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins