(776g) Monocyte Chemoattractant Protein-1 Static Concentration Gradient in a 3D Collagen Matrix and Its Haptotactic Effect On Monocyte Migration

Atherosclerosis is known as an inflammatory disease which is initiated by the accumulation of lipid substances in the subendothelial layer of major arteries, followed by adhesion of monocytes and lymphocytes to endothelial cells and their subsequent migration across the endothelial layer to the extracellular matrix (ECM). This adhesion and transmigration involves several steps, which are mediated by bioactive molecules named chemotactic cytokines (chemokines). Monocyte Chemoattractant Protein-1 (MCP-1) is one chemokine that plays an important role in monocyte trafficking across the endothelial layer. Many studies investigate the effect of soluble concentration gradients of chemokines, such as MCP-1, on monocyte migration by using a 2D experimental system.  Studies have shown that soluble concentration gradients of chemokines drive, and possibly control cell migration. Recently, it was hypothesized that MCP-1 can bind with collagen, which is a major protein in the extracellular matrix (ECM). A 2D system may not adequately predict in vivo cell behavior due to the lack of the third dimension that is important for the creation of MCP-1 binding reaction in the ECM. A 3D tissue model consisting of a collagen matrix would be a better experimental model for studying the formation of MCP-1 static concentration gradient within the ECM. The goal of this research is to confirm the formation of an MCP-1 static concentration gradient within a simplified 3D vascular tissue model and examine its haptotactic effect on monocyte migration. The experimental results show that the 3D tissue model pre-treated with MCP-1 had a significant increase in the number of migrated monocytes in comparison with the control group lacking the pre-treatment. Also, when an MCP-1 antibody was used to block the MCP-1 within the collagen matrix, there was no significant difference between the number of migrated monocytes compared to the control group that was not treated with MCP-1. Furthermore, it is shown that the haptotactic (static) gradient of MCP-1 had the same effect and potency on monocyte migration as the chemotactic (soluble + static) gradient of MCP-1. The results suggest that the effect of the static MCP-1 concentration gradient on monocyte transmigration is stronger than the soluble MCP-1 concentration gradient in the collagen matrix. The results of this research will provide new information about the relationship between MCP-1 concentration gradients and monocyte transendothelial migration, and will lead to the development of an improved model to study transendothelial monocyte migration associated with inflammation.