XXXX primes neutrophils to undergo NETosis, which impairs wound healing.

@entity1 @entity32 @entity6 @entity73107 @entity19 @entity164 @entity9828 @entity130
@entity130 is impaired in @entity6 , resulting in significant morbidity and mortality. Neutrophils are the main leukocytes involved in the early phase of healing. As part of their anti-microbial defense, neutrophils form extracellular traps (NETs) by releasing decondensed chromatin lined with cytotoxic proteins. NETs, however, can also induce tissue damage. Here we show that neutrophils isolated from type 1 and type 2 @entity6 @entity1 and @entity19 were primed to produce NETs (a process termed NETosis). Expression of peptidylarginine deiminase 4 (PAD4, encoded by @entity73107 in @entity19 ), an enzyme important in chromatin decondensation, was elevated in neutrophils from individuals with @entity6 . When subjected to excisional skin wounds, @entity164 ( @entity164 ) @entity19 produced large quantities of NETs in wounds, but this was not observed in @entity73107 (-/-) @entity19 . In @entity6 @entity19 , higher levels of citrullinated histone H3 (H3Cit, a NET marker) were found in their wounds than in normoglycemic @entity19 and healing was delayed. @entity130 was accelerated in @entity73107 (-/-) @entity19 as compared to @entity164 @entity19 , and it was not compromised by @entity6 . @entity9828 , which disrupts NETs, accelerated wound healing in @entity6 and normoglycemic @entity164 @entity19 . Thus, NETs impair wound healing, particularly in @entity6 , in which neutrophils are more susceptible to NETosis. Inhibiting NETosis or cleaving NETs may improve wound healing and reduce NET-driven chronic @entity32 in @entity6 .
