Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expression.
During the resolution phase of inflammation, the 'corpses' of apoptotic leukocytes are gradually cleared by macrophages. Here we report that during the resolution of peritonitis, the CCR5 chemokine receptor ligands CCL3 and CCL5 persisted in CCR5-deficient mice. CCR5 expression on apoptotic neutrophils and activated apoptotic T cells sequestered and effectively cleared CCL3 and CCL5 from sites of inflammation. CCR5 expression on late apoptotic human polymorphonuclear cells was downregulated by proinflammatory stimuli, including tumor necrosis factor, and was upregulated by 'proresolution' lipid mediators, including lipoxin A4, resolvin E1 and protectin D1. Our results suggest that CCR5+ apoptotic leukocytes act as 'terminators' of chemokine signaling during the resolution of inflammation.
Ariel
Amiram
A
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Fredman
Gabrielle
G
Sun
Yee-Ping
YP
Kantarci
Alpdogan
A
Van Dyke
Thomas E
TE
Luster
Andrew D
AD
Serhan
Charles N
CN
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D065100:CCR5 Receptor Antagonists; D018925:Chemokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D019713:Receptors, CCR5 / Q000096:biosynthesis* / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D065100:CCR5 Receptor Antagonists; D018925:Chemokines; D018836:Inflammation Mediators; D019713:Receptors, CCR5