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.
Bibliographical noteFunding Information:
We thank M.H. Small for assistance in manuscript preparation, and J. Deady for technical assistance. Supported by the US National Institutes of Health (GM38765, DK-074448 and P50-DE016191 to C.N.S., and DK-074449 to A.D.L.) and the Arthritis Foundation (A.A.).
ASJC Scopus subject areas
- Immunology and Allergy