Fig. 3: The interplay between DNases, the actin-scavenger system and the fibrinolytic system during injury.

The interplay between the diverse mechanisms facilitating the clearance of necrotic cell debris is complex. During injury, the actin-scavenger system can become saturated, increasing circulating actin levels. This results in the inhibition of DNase 1 activity, thus impeding the internucleosomal cleavage of necrotic DNA. The activity of the fibrinolytic system, particularly plasmin, can be altered depending on the severity of injury. Plasmin enhances DNase 1 activity while hampering DNase 1L3 activity through the degradation of DNA-binding proteins. Histones and actin can both interact with fibrin, increasing resistance of the fibrin network to fibrinolysis. Additionally, actin acts as a noncompetitive inhibitor of plasmin, further reducing fibrinolysis.