1. Staphylococcus aureus extracellular adherence protein (Eap) reduces immune cell phenotype in developing but not in established atherosclerotic lesions.
- Author
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Salzmann M, Platzer H, Mussbacher M, Derler M, Lenz M, Haider P, Brekalo M, Kral-Pointner JB, Kastl S, Speidl WS, Preissner KT, Schubert U, Bischoff M, Uhrin P, Wojta J, and Hohensinner PJ
- Subjects
- Mice, Animals, Intercellular Adhesion Molecule-1 genetics, Staphylococcus aureus metabolism, Endothelial Cells metabolism, Lymphocyte Function-Associated Antigen-1 genetics, Phenotype, Atherosclerosis, Plaque, Atherosclerotic
- Abstract
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 β2 ) and lymphocyte function-associated antigen 1 (LFA-1, αL β2 ), 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.)- Published
- 2023
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