Effect of hyperglycemia on leukocyte migration and differentiation in a novel three-dimensional tissue model.

摘要

Leukocytes are known to migrate across an endothelium continuously but this migration is enhanced in case of certain inflammatory signals, such as those associated with hyperglycemia. Currently, there have not been any studies to characterize the transient behavior of leukocyte migration and differentiation in response to hyperglycemia. A 3D human vascular tissue model has been developed to investigate the effect of high glucose concentrations first, on endothelial cell behavior and second, on leukocyte trafficking and differentiation. The 3D tissue model was exposed to varying glucose concentrations of 5.6, 15, and 30 mM for an optimal incubation time of nine hours. The effect of glucose on endothelial cell viability, expression of cell adhesion molecules (CAMs) on endothelial cells, and leukocyte trafficking and differentiation within the 3D tissue model was studied. Endothelial cells incubated with high glucose concentrations for nine hours showed no significant decrease in cell viability compared to cells incubated at a normal glucose concentration of 5.6 mM. Among the different CAMs tested, only VCAM-1 showed a significant change in expression in response to the high glucose concentrations. An increase in glucose concentration affected leukocyte migration and differentiation patterns within the 3D tissue model. There were significant increases in certain cell populations for the 3D tissue model exposed to 30 mM glucose, compared to the control at 5.6 mM. For the cells undergoing initial migration across the endothelium into the subendothelial space, T cell and monocyte cell populations increased by 140% and 75%, respectively. For the cells undergoing reverse-transmigration across the endothelium, the immature dendritic cell population increased by 80%. For the cells remaining within the subendothelial space, T cell and macrophage cell populations increased by 380% and 100%, respectively.