Department of Chemistry, University of British Columbia Okanagan, 3247 University Way, Kelowna, BC, V1V 1V7, Canada.
Faculty of Medicine, University of British Columbia, Kelowna, BC, Canada.
BMC Res Notes. 2022 Dec 3;15(1):355. doi: 10.1186/s13104-022-06248-0.
Type 2 diabetes mellitus (T2D) is the result of a dysregulation of insulin production and signalling, leading to an increase in both glucose concentration and pro-inflammatory cytokines such as interleukin (IL)-6 and tumour necrosis factor (TNF)-α. Previous work showed that T2D patients exhibited immune dysfunction associated with increased adhesion molecule expression on endothelial cell surfaces, accompanied by decreased neutrophil rolling velocity on the endothelial cell surface. Changes in cell rolling adhesion have direct vascular and immune complications such as atherosclerosis and reduced healing time in T2D patients. While previous studies focused primarily on how endothelial cells affect neutrophil rolling under T2D conditions, little is known about changes to neutrophils that affect their rolling. In this study, we aim to show how the rolling behaviour of neutrophils is affected by T2D conditions on a controlled substrate.
We found that neutrophils cultured in T2D-serum mimicking media increased cell rolling velocity compared to neutrophils under normal conditions. Specifically, glucose alone is responsible for higher rolling velocity. While cytokines further increase the rolling velocity, they also reduce the cell size. Both glucose and cytokines likely reduce the function of P-selectin Glycoprotein Ligand-1 (PSGL-1) on neutrophils.
2 型糖尿病（T2D）是胰岛素产生和信号转导失调的结果，导致葡萄糖浓度和促炎细胞因子（如白细胞介素（IL）-6 和肿瘤坏死因子（TNF）-α）增加。先前的工作表明，T2D 患者表现出与内皮细胞表面粘附分子表达增加相关的免疫功能障碍，同时内皮细胞表面的中性粒细胞滚动速度降低。细胞滚动黏附的变化与血管和免疫并发症直接相关，如动脉粥样硬化和 T2D 患者的愈合时间缩短。虽然以前的研究主要集中在 T2D 条件下内皮细胞如何影响中性粒细胞的滚动，但对于影响其滚动的中性粒细胞变化知之甚少。在这项研究中，我们旨在展示在受控基质上 T2D 条件如何影响中性粒细胞的滚动行为。
我们发现，与正常条件下的中性粒细胞相比，在 T2D 血清模拟培养基中培养的中性粒细胞的细胞滚动速度增加。具体来说，仅葡萄糖就负责更高的滚动速度。虽然细胞因子进一步增加了滚动速度，但它们也减小了细胞大小。葡萄糖和细胞因子都可能降低中性粒细胞上 P 选择素糖蛋白配体-1（PSGL-1）的功能。
