The Effect of Pro-Inflammatory Conditions on Neutrophil Rolling Adhesion

Abstract Objective: Type 2 diabetes mellitus (T2D) is the result of a dysregulation of insulin concentrations and signaling, leading to an increase in both glucose concentration and proinflammatory cytokines such as interleukin (IL)-6 and tumor 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 decreased healing time seen in T2D patients. While previous studies focused primarily on how endothelial cells affect neutrophil rolling under T2D conditions, little is known on changes to neutrophils that affect their rolling. In this study, we aim to show how the rolling behaviour of neutrophils are affected by T2D conditions on a controlled substrate. Results: We found that neutrophils cultured in T2D-serum mimicking media showed an increase in 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. It is likely that both glucose and cytokines reduce the PSGL-1 expression level on neutrophils.