Nature Immunology
- 7, 1209 - 1216 (2006)
Published online: 1 October 2006; | doi:10.1038/ni1392
Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expressionAmiram Ariel1, Gabrielle Fredman1, Yee-Ping Sun1, Alpdogan Kantarci2, Thomas E Van Dyke2, Andrew D Luster3 & Charles N Serhan11
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. 2
Department of Periodontology and Oral Biology, Goldman School of Dental Medicine, Boston University, Boston, Massachusetts, 02118, USA. 3
Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Correspondence should be addressed to Charles N Serhan cnserhan@zeus.bwh.harvard.edu 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.
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