Identification Of "Antigen-Specific" Neutrophils In Atherosclerosis Patients That Compromise Vascular Endothelial Barrier Function

AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH(2020)

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摘要
The vascular endothelial barrier dysfunction is associated with the pathogenesis of many cardiovascular diseases, such as atherosclerosis (AS). This study aims to identify specific antigen (Ag, in short)-specific polymorphonuclear neutrophils (PMN) in AS patients and to investigate the role of "Ag-specific" PMN activation in causing vascular endothelial barrier dysfunction. In this study, PMNs were isolated from blood samples collected from patients with AS and analyzed with immunological approaches. Human umbilical vein endothelial cells (HUVEC) monolayers were used as a vascular endothelial barrier model. The results showed that "Ag-specific" PMNs were identified in the blood of 50 AS patients. This subset of PMN was featured as the FcyRl and specific IgG (slgG) complexes on the cell surface; exposure to specific Ags triggered the "Ag-specific" PMNs to release proinflammatory cytokines. PMN-derived cytokine levels in the serum were positively correlated with the serum levels of slgG in AS patients. Exposure of naive PMNs to slgG formed FcyRl and slgG complexes on the surface; this conferred PMNs the property to be recognized and activated by specific Ag. Stimulation of "Ag-specific" PMN activated the mitogen-activated protein kinase and the activities of nuclear factor activated T cells and promoted the gene transcription of tumor necrosis factor-a. Coculture of "Ag-specific" PMNs and HUVEC monolayers in the presence of specific Ag resulted in the HUVEC monolayer barrier dysfunction. In conclusion, "Ag-specific" PMNs were identified in AS patients. Activation of the PMNs compromised vascular endothelial barrier function. Therefore, to regulate the "Ag-specific" PMN's activities may have translational potential in the treatment of AS.
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关键词
Vascular endothelium, endothelial barrier, neutrophil, immunity, atherosclerosis
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