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Immunoregulatory Siglec ligands are abundant in human and mouse aorta and are up-regulated by high glucose
- Source :
- Life sciences. 216
- Publication Year :
- 2018
-
Abstract
- Aim Inflammation is a driving force in development of atherosclerosis, and hyperglycemia is a significant risk factor for angiopathy. Siglec-9, expressed on human neutrophils and macrophages, engages specific glycan ligands on tissues to diminish ongoing inflammation. Materials and method Siglec-9 ligands on human aorta were characterized and the effects of high glucose exposure on the expression of ligands for Siglec-9 on human umbilical vein endothelial cells (HUV-EC-C) in vitro and ligands for the comparable siglec (Siglec-E) on mouse aorta in vivo were studied. Key findings Siglec-9 ligands were expressed broadly on human aorta, as well as on HUV-EC-C. Siglec-9 ligands on HUV-EC-C were sharply up-regulated under high glucose exposure in vitro, as were Siglec-E ligands on the aortas of hyperglycemic mice. Exposure of HUV-EC-C to high-glucose resulted in consistent inhibitory changes in co-cultured macrophages including increased apoptosis and decreased phagocytosis. Control of Siglec-9 ligand expression on HUV-EC-C was downstream of changes in an enzyme involved in their biosynthesis, UDP-galactose-4-epimerase (GALE) and increased cellular N-acetylgalactosamine. The alteration of GALE was associated with the regulatory microRNA hsa-let-7f. Significance We conclude that exposure to high-glucose results in up-regulation of immune inhibitory Siglec-9 sialoglycan ligands on aorta and HUV-EC-C cells downstream of altered GALE and GalNAc expression, resulting in up-regulation of apoptosis and decrease of phagocytic activity of macrophages. Changes in Siglec-9 sialoglycan ligand expression on vascular endothelial cells may be a natural response to the initial steps of atherosclerosis and might be a potential target to regulate inflammation in diabetic angiopathy.
- Subjects :
- 0301 basic medicine
Male
Inflammation
Apoptosis
Ligands
030226 pharmacology & pharmacy
General Biochemistry, Genetics and Molecular Biology
Umbilical vein
03 medical and health sciences
Mice
UDPglucose 4-Epimerase
0302 clinical medicine
Immune system
Downregulation and upregulation
In vivo
Antigens, CD
medicine
Human Umbilical Vein Endothelial Cells
Animals
Humans
General Pharmacology, Toxicology and Pharmaceutics
Aorta
Sialic Acid Binding Immunoglobulin-like Lectins
Mice, Inbred BALB C
Chemistry
Macrophages
SIGLEC
General Medicine
respiratory system
In vitro
Cell biology
Up-Regulation
Antigens, Differentiation, B-Lymphocyte
030104 developmental biology
Glucose
medicine.symptom
Subjects
Details
- ISSN :
- 18790631
- Volume :
- 216
- Database :
- OpenAIRE
- Journal :
- Life sciences
- Accession number :
- edsair.doi.dedup.....1b7c2aaa5f2dccaed96d9a910649176a