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Hoffmann, A.L.C.* ; Hauck, S.M. ; Deeg, C.A.* ; Degroote, R.L.*

Pre-activated granulocytes from an autoimmune uveitis model show divergent pathway activation profiles upon IL8 stimulation in vitro.

Int. J. Mol. Sci. 23:9555 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
In the pathophysiology of autoimmune-mediated uveitis, granulocytes have emerged as possible disease mediators and were shown to be pre-activated in equine recurrent uveitis (ERU), a spontaneous disease model. We therefore used granulocytes from ERU horses to identify early molecular mechanisms involved in this dysregulated innate immune response. Primary granulocytes from healthy and ERU horses were stimulated with IL8, and cellular response was analyzed with differential proteomics, which revealed significant differences in protein abundance of 170 proteins in ERU. Subsequent ingenuity pathway analysis identified three activated canonical pathways "PKA signaling", "PTEN signaling" and "leukocyte extravasation". Clustered to the leukocyte extravasation pathway, we found the membrane-type GPI-anchored protease MMP25, which was increased in IL8 stimulated ERU granulocytes. These findings point to MMP25 as a possible regulator of granulocyte extravasation in uveitis and a role of this molecule in the impaired integrity of the blood-retina-barrier. In conclusion, our analyses show a clearly divergent reaction profile of pre-activated granulocytes upon IL8 stimulation and provide basic information for further in-depth studies on early granulocyte activation in non-infectious ocular diseases. This may be of interest for the development of new approaches in uveitis diagnostics and therapy. Raw data are available via ProteomeXchange with identifier PXD013648.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Eru ; Il8 ; Pmn ; Extravasation ; Pre-activated Granulocytes
ISSN (print) / ISBN 1422-0067
e-ISSN 1661-6596
Zeitschrift International Journal of Molecular Sciences
Quellenangaben Band: 23, Heft: 17, Seiten: , Artikelnummer: 9555 Supplement: ,
Verlag MDPI
Verlagsort Basel
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) CF Metabolomics & Proteomics (CF-MPC)
Förderungen Deutsche Forschungsgemeinschaft