Figure 4.

I/R injury to hepatocytes is mediated by immune cells. The initial immune cascade is caused by the expression of DAMP/PAMP on the surfaces of cells, including hepatocytes. The resident macrophages, Kupffer cells, and dendritic cells express TLRs that bind DAMPs/PAMPs and activate the immune cells, releasing ROS, cytokines, and chemokines. Reperfusion activates adaptive immune cells (CD4+ T cells, γδ T cells, and NKT cells) and innate immune cells (primarily neutrophils) that are recruited to the site of tissue injury. The cells release a second cascade of mediators. TNF-α is produced in both the initial and secondary cascades. Hepatocytes express TNFRI in response to the massive influx of TNF-α.