Figure 2

Modulation of inflammation by fibrin(ogen) and their degradation products. Following trauma and/or infection, tissue factor is released and induces coagulation. Fibrinogen is converted to fibrin, which in turn is degraded by plasmin. Fibrin(ogen) modulates the inflammatory response by affecting leukocyte migration, but also by induction of cytokine/chemokine expression mostly via Mac-1 signaling. Fibrin fragment E also induces cytokine expression and leukocyte recruitment/migration by binding to VE-cadherin, which is inhibited by Bβ15–42. Furthermore, Bβ15–42 preserves stress- induced endothelial barrier function by inhibiting Rho-kinase activation and subsequent junction opening. NO, nitric oxide; Mac-1, macrophage antigen 1; PI3K, phosphoinositide-3-kinase; TNFα, tumor necrosis factor-α.