Regulation of macrophage activation in the liver after acute injury: Role of the fibrinolytic system

Figure 2 Treatment of these cells with plasmin increased expression of tumor necrosis factor-α, Ccl2, Cxcl1 and Cxcl2 consistent with the hypothesis that plasmin directly activates Kupffer cells. (1) After acetaminophen overdose, plasmin is generated and high-mobility group B1 is released from dead hepatocytes. These synergize to stimulate release of (2) pro-inflammatory cytokines, including Ccl2, from Kupffer cells. (3) Ccl2 stimulates recruitment of proinflammatory monocytes that accumulate at the periphery of the necrotic lesion. (4) Plasmin generation stimulates degradation of fibrin and/or activate matrix metalloproteinases that facilitate trafficking of the monocytes into the injured region. (5) The monocytes phagocytose dead cells which contributes to their conversion of pro-restorative macrophages. Ccl2: Chemokine, chemokine ligand 2; HMGB1: High-mobility group B1.