Celiac disease patient IgA antibodies induce endothelial adhesion and cell polarization defects via extracellular transglutaminase 2

Cristina A. Nadalutti, Ilma R. Korponay-Szabó, Katri Kaukinen, Martin Griffin, Markku Mäki, Katri Lindfors

Research output: Contribution to journalArticle

Abstract

We have recently found that celiac disease patient serum-derived autoantibodies targeted against transglutaminase 2 interfere with several steps of angiogenesis, including endothelial sprouting and migration, though the mechanism involved remained to be fully characterized. This study now investigated the processes underlying the antiangiogenic effects exerted by celiac disease patient antibodies on endothelial cells, with particular regard to the adhesion, migration, and polarization signaling pathway. We observed that celiac IgA reduced endothelial cell numbers by affecting adhesion without increasing apoptosis. Endothelial cells in the presence of celiac IgA showed weak attachment, a high susceptibility to detach from fibronectin, and a disorganized extracellular matrix due to a reduction of protein cross-links. Furthermore, celiac patient IgA led to secretion of active transglutaminase 2 from endothelial cells into the culture supernatants. Additionally, cell surface transglutaminase 2 mediated integrin clustering in the presence of celiac IgA was coupled to augmented expression of ß1-integrin. We also observed that celiac patient IgA-treated endothelial cells had migratory defects and a less polarized phenotype when compared to control groups, and this was associated with the RhoA signaling pathway. These biological effects mediated by celiac IgA on endothelial cells were partially influenced but not completely abolished by R281, an irreversible extracellular transglutaminase 2 enzymatic activity inhibitor. Taken together, our results imply that celiac patient IgA antibodies disturb the extracellular protein cross-linking function of transglutaminase 2, thus altering cell-extracellular matrix interactions and thereby affecting endothelial cell adhesion, polarization, and motility.
Original languageEnglish
Pages (from-to)1315-1326
Number of pages12
JournalCellular and Molecular Life Sciences
Volume71
Issue number7
Early online date28 Aug 2013
DOIs
Publication statusPublished - Apr 2014

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Celiac Disease
Abdomen
Immunoglobulin A
Endothelial Cells
Antibodies
Integrins
Extracellular Matrix
transglutaminase 2
Fibronectins
Cell Adhesion
Autoantibodies
Cell Movement
Cluster Analysis
Cell Culture Techniques
Cell Count
Apoptosis
Phenotype
Control Groups
Serum
Proteins

Cite this

Nadalutti, Cristina A. ; Korponay-Szabó, Ilma R. ; Kaukinen, Katri ; Griffin, Martin ; Mäki, Markku ; Lindfors, Katri. / Celiac disease patient IgA antibodies induce endothelial adhesion and cell polarization defects via extracellular transglutaminase 2. In: Cellular and Molecular Life Sciences. 2014 ; Vol. 71, No. 7. pp. 1315-1326.
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Celiac disease patient IgA antibodies induce endothelial adhesion and cell polarization defects via extracellular transglutaminase 2. / Nadalutti, Cristina A.; Korponay-Szabó, Ilma R.; Kaukinen, Katri; Griffin, Martin; Mäki, Markku; Lindfors, Katri.

In: Cellular and Molecular Life Sciences, Vol. 71, No. 7, 04.2014, p. 1315-1326.

Research output: Contribution to journalArticle

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