ROLE OF PEPTIDYLARGININE DEIMINASE AND NEUTROPHIL EXTRACELLULAR TRAPS IN INJURIES: FUTURE NOVEL DIAGNOSTICS AND THERAPEUTIC TARGETS.

ABSTRACT: Injuries lead to an early systemic inflammatory state with innate immune system activation. Neutrophil extracellular traps (NETs) are a complex of chromatin and proteins released from the activated neutrophils. Although initially described as a response to bacterial infections, NETs have also been identified in the sterile postinjury inflammatory state. Peptidylarginine deiminases (PADs) are a group of isoenzymes that catalyze the conversion of arginine to citrulline, termed citrullination or deimination. PAD2 and PAD4 have been demonstrated to play a role in NET formation through citrullinated histone 3. PAD2 and PAD4 have a variety of substrates with variable organ distribution. Preclinical and clinical studies have evaluated the role of PADs and NETs in major trauma, hemorrhage, burns, and traumatic brain injury. Neutrophil extracellular trap formation and PAD activation have been shown to contribute to the postinjury inflammatory state leading to a detrimental effect on organ systems. This review describes our current understanding of the role of PAD and NET formation following injury and burn. This is a new field of study, and the emerging data appear promising for the future development of targeted biomarkers and therapies in trauma.