Staphylococcus aureus extracellular adherence protein (Eap) reduces immune cell phenotype in developing but not in established atherosclerotic lesions.

Autor: Salzmann M; Department of Internal Medicine II/Division of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria; Ludwig Boltzmann Institute for Cardiovascular Research, Waehringer Guertel 18-20, 1090 Vienna, Austria. Electronic address: manuel.salzmann@meduniwien.ac.at., Platzer H; Department of Internal Medicine II/Division of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Electronic address: harald.platzer@meduniwien.ac.at., Mussbacher M; Department of Pharmacology and Toxicology, University of Graz, Humboldtstraße 46, 8010 Graz, Austria. Electronic address: marion.mussbacher@uni-graz.at., Derler M; Department of Pharmacology and Toxicology, University of Graz, Humboldtstraße 46, 8010 Graz, Austria. Electronic address: martina.derler@uni-graz.at., Lenz M; Department of Internal Medicine II/Division of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Electronic address: max.lenz@meduniwien.ac.at., Haider P; Department of Internal Medicine II/Division of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Electronic address: patrick.haider@meduniwien.ac.at., Brekalo M; Department of Internal Medicine II/Division of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Electronic address: mira.brekalo@meduniwien.ac.at., Kral-Pointner JB; Department of Internal Medicine II/Division of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria; Ludwig Boltzmann Institute for Cardiovascular Research, Waehringer Guertel 18-20, 1090 Vienna, Austria. Electronic address: julia.pointner@meduniwien.ac.at., Kastl S; Department of Internal Medicine II/Division of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Electronic address: stefan.kastl@meduniwien.ac.at., Speidl WS; Department of Internal Medicine II/Division of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria; Ludwig Boltzmann Institute for Cardiovascular Research, Waehringer Guertel 18-20, 1090 Vienna, Austria. Electronic address: walter.speidl@meduniwien.ac.at., Preissner KT; Department of Cardiology, Kerckhoff Heart Research Institute, Justus-Liebig-University, Aulweg 129, 35392 Giessen, Germany; Department of Biochemistry, Medical Faculty, Justus-Liebig-University, Friedrichstrasse 24, 35392 Giessen, Germany. Electronic address: klaus.t.preissner@biochemie.med.uni-giessen.de., Schubert U; Department of Biochemistry, Medical Faculty, Justus-Liebig-University, Friedrichstrasse 24, 35392 Giessen, Germany. Electronic address: uwe.schubert@biochemie.med.uni-giessen.de., Bischoff M; Institute of Medical Microbiology and Hygiene, Saarland University, Kirrberger Straße 100, 66424 Homburg, Germany. Electronic address: markus.bischoff@uks.eu., Uhrin P; Center for Physiology and Pharmacology, Schwarzspanierstraße 17A, 1090 Vienna, Austria. Electronic address: pavel.uhrin@meduniwien.ac.at., Wojta J; Department of Internal Medicine II/Division of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria; Ludwig Boltzmann Institute for Cardiovascular Research, Waehringer Guertel 18-20, 1090 Vienna, Austria. Electronic address: johann.wojta@meduniwien.ac.at., Hohensinner PJ; Ludwig Boltzmann Institute for Cardiovascular Research, Waehringer Guertel 18-20, 1090 Vienna, Austria; Center for Biomedical Research, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Electronic address: philipp.hohensinner@meduniwien.ac.at.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2023 Mar; Vol. 1869 (3), pp. 166616. Date of Electronic Publication: 2022 Dec 10.
DOI: 10.1016/j.bbadis.2022.166616
Abstrakt: Atherosclerosis is a chronic, inflammatory disease of the vessel wall where triggered immune cells bind to inflamed endothelium, extravasate and sustain local inflammation. Leukocyte adhesion and extravasation are mediated by adhesion molecules expressed by activated endothelial cells, like intercellular adhesion molecule 1 (ICAM-1). Extracellular adherence protein (Eap) from Staphylococcus aureus binds to a plethora of extracellular matrix proteins, including ICAM-1 and its ligands macrophage-1 antigen (Mac-1, α M β 2 ) and lymphocyte function-associated antigen 1 (LFA-1, α L β 2 ), thereby disrupting the interaction between leukocytes and endothelial cells. We aimed to use Eap to inhibit the interaction of leukocytes with activated endothelial cells in settings of developing and established atherosclerosis in apolipoprotein E (ApoE) deficient mice on high-fat diet. In developing atherosclerosis, Eap treatment reduced circulating platelet-neutrophil aggregates as well as infiltration of T cells and neutrophils into the growing plaque, accompanied by reduced formation of neutrophil extracellular traps (NETs). However, plaque size did not change. Intervention treatment with Eap of already established plaques did not result in cellular or morphological plaque changes, whereas T cell infiltration was increased and thereby again modulated by Eap. We conclude that although Eap leads to cellular changes in developing plaques, clinical implications might be limited as patients are usually treated at a more advanced stage of disease progression. Hence, usage of Eap might be an interesting mechanistic tool for cellular infiltration during plaque development in basic research but not a clinical target.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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