Dying and necrotic neutrophils are anti-inflammatory secondary to the release of alpha-defensins.
Neutrophils are recruited to sites of injury but their timely removal is thought to be vital to prevent exacerbating inflammation. In addition, the recognition of apoptotic cells by cells of the innate immune system provides potent anti-inflammatory and anti-immunogenic signals. In this article, we describe how human neutrophils dying by apoptosis or necrosis release anti-inflammatory peptides, the alpha-defensins. This family of small cationic peptides effectively inhibits the secretion of multiple proinflammatory cytokines and NO from macrophages, the main innate immune cell found at sites of chronic inflammation. In addition, the systemic administration of necrotic neutrophil supernatants and alpha-defensins protects mice from a murine model of peritonitis. Hence. their effects may be far-reaching and serve to kill microbes while regulating a potentially tissue-destructive inflammatory response.
Miles
Katherine
K
The Queen's Medical Research Institute, College of Science and Engineering, University of Edinburgh, Edinburgh, United Kingdom.
Clarke
David J
DJ
Lu
Wuyuan
W
Sibinska
Zaneta
Z
Beaumont
Paula E
PE
Davidson
Donald J
DJ
Barr
Tom A
TA
Campopiano
Dominic J
DJ
Gray
Mohini
M
D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000188:drug therapy; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009336:Necrosis; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D010538:Peritonitis / Q000188:drug therapy; D023084:alpha-Defensins / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use
D016207:Cytokines; D023084:alpha-Defensins; D009569:Nitric Oxide