Skip to main content
. Author manuscript; available in PMC: 2024 Feb 1.
Published in final edited form as: Shock. 2023 Jan 5;59(2):247–255. doi: 10.1097/SHK.0000000000002052

FIGURE 2. The role of PADs and NETs in injury.

FIGURE 2

A. Peptidylarginine deiminase 4 (PAD4) mediates the citrullination of histones in neutrophils resulting in NETosis. PADs and NETs have been demonstrated to facilitate the formation of thrombosis after trauma. NETs emit a fibrous mesh that provides an intravascular scaffold for platelets, von Willebrand Factor (vWF), fibronectin, and fibrinogen adherence. Histones released during NETosis induce platelet aggregation through interactions with toll-like receptor 2 (TLR2) and 4 (TLR4) on platelets. PAD4 released during NETosis citrullinates ADAMTS13 impairing its ability to cleave vWF-platelet strings. B. Following a burn or wound, neutrophils infiltrate into the wound tissue and undergo NETosis, which can impair wound healing. A proposed mechanism is through a decreased collagen I to III ratio (higher proportion of immature fibers, collagen III) with poor wound alignment and the formation of microthrombi. C and D. NETosis has been observed in the damaged tissue after traumatic brain injury (TBI) and spinal cord injury (SCI). While PAD inhibitors or DNase1 have been shown to alleviate the local tissue damage, the role of PADs and NETs in TBI and SCI remain to be elucidated.