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The influence of hyperglycemia on neutrophil extracellular trap formation and endothelial glycocalyx damage in a mouse model of type 2 diabetes
Author(s) -
Hirota Tatsuhiko,
Levy Jerrold H.,
Iba Toshiaki
Publication year - 2020
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/micc.12617
Subject(s) - neutrophil extracellular traps , glycocalyx , diabetes mellitus , integrin alpha m , immunology , granulocyte , medicine , myeloperoxidase , endocrinology , inflammation , chemistry , flow cytometry
Objectives Hyperglycemia induces vascular dysfunction that is thought to be initiated by neutrophils. Neutrophil activation produces endothelial injury by pathways that include NETosis, a type of specific cell death. In this study, we investigated the effects of hyperglycemia on neutrophil activation, cell death, NETosis, and endothelial glycocalyx damage using a mouse diabetes model. Methods We used db/db mice as a type 2 diabetes model, and C57BL/6 mice were the controls. At 5, 8, and 12 weeks of age, the proportion of CD11b + granulocytes/monocytes, neutrophil extracellular trap (NET)‐forming granulocytes/monocytes, and damaged and nonviable granulocytes/monocytes was analyzed. In addition, serum levels of high mobility group box 1, histone H3, and glycocalyx components that included syndecan‐1 and hyaluronan were measured. Results In diabetic mice, we observed an increased proportion of CD11b + granulocytes/monocytes. The proportion of NET‐forming granulocytes/monocytes increased from the early stages of the experiments. The proportions of damaged and nonviable granulocytes/monocytes increased over time. In the 12‐week‐old diabetic mice, serum histone H3 levels increased. Circulating levels of syndecan‐1 and hyaluronan decreased over time and were lower in diabetic mice. Conclusion Neutrophil activation and cell death induce endothelial glycocalyx damage, and NET formation also participates in the mechanisms of vascular injury in type 2 diabetes.