The emerging roles of neutrophil extracellular traps in wound healing

Abstract

Delayed wound healing causes problems for many patients both physically and psychologically, contributing to pain, economic burden, loss of function, and even amputation. Although many factors affect the wound healing process, abnormally prolonged or augmented inflammation in the wound site is a common cause of poor wound healing. Excessive neutrophil extracellular trap (NET) formation during this phase may amplify inflammation and hinder wound healing. However, the roles of NETs in wound healing are still unclear. Herein, we briefly introduce NET formation and discuss the possible NET-related mechanisms in wound healing. We conclude with a discussion of current studies, focusing on the roles of NETs in diabetic and normoglycemic wounds and the effectiveness of NET-targeting treatments in wound healing.

The role of neutrophil extracellular traps in acute lung injury

“…However, directly targeting NET generation by the genetic deletion or pharmacological inhibition of PAD4 prevented alloimmune responses and allograft rejection (136). The unintended consequences associated with NET digestion have been increasingly described in different animal models, raising the question of whether it is more effective to prevent NETosis in lieu of DNase treatment (137). For example, NETs have been described to merge in high-density structures named aggNETs, which are thought to prevent bystander tissue injury as well as contribute to wound healing and inflammation resolution through driving the proteolytic degradation of cytokines and histones (138)(139)(140).…”

Cutaneous Wound Healing: A Review about Innate Immune Response and Current Therapeutic Applications

“…This process of defense against infection has been first described in neutrophils under the term Neutrophil Extracellular Traps (NETs), corresponding to the NETosis mechanism [ 87 ]. NETosis has been shown to play a potent role in wound healing [ 88 ]. Such process of defense is also used by macrophages in response to various stimuli, known as Macrophage Extracellular Traps (osis) (METosis) [ 89 ].…”

T Cell Extracellular Traps: Tipping the Balance Between Skin Health and Disease

“…Degradation of the DNA backbone of ETs triggers the release of antibacterial proteins and upregulates inflammatory cytokines, such as type I interferon, IL-17, and IL-8 ( 170 – 173 ). While hyperinflammation is important for fighting infections, after injury, hypoinflammation is needed during tissue healing and repair ( 174 ). Therefore, overabundance of TETs during repair is counterproductive, unless there is continued need for protecting against inadvertent infections.…”