Liver ischemia/reperfusion (I/R) injury is a pathophysiological process in which the hypoxic insult is further accentuated by restoration of blood flow to the compromised organ. Liver I/R injury is linked to leukocyte infiltration, release of free radicals and of cytokines. The mechanisms involved in leukocyte recruitment to inflammatory sites in liver are poorly understood. Overall, leukocytes circulate continuously in the blood, and their migration across endothelial barriers or extracellular matrix (ECM) proteins to inflamed tissues is a complex process dependent on the coordination of cellular adhesion-release steps and focal matrix degradation. While adhesion molecules are critical to the successful promotion of leukocyte transmigration by providing leukocyte attachment to the vascular endothelium, matrix metalloproteinases (MMPs) are important for facilitating leukocyte movement across vascular barriers. Our research is primarily focused in dissecting the function of key ECM proteins and MMPs upon leukocyte migration and activation in hepatic I/R injury.
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