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 apoptoti...

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Bibliographic Details
Published in:Nature Immunology 2006-11, Vol.7 (11), p.1209-1216
Main Authors: Serhan, Charles N, Ariel, Amiram, Fredman, Gabrielle, Sun, Yee-Ping, Kantarci, Alpdogan, Van Dyke, Thomas E, Luster, Andrew D
Format: Article
Language:English
Subjects:
Animals
Apoptosis - immunology
Biomedical and Life Sciences
Biomedicine
CCR5 Receptor Antagonists
Chemokines - metabolism
Female
Humans
Immune response
Immunology
Infectious Diseases
Inflammation Mediators - antagonists & inhibitors
Inflammation Mediators - metabolism
Inflammation Mediators - physiology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Neutrophils - immunology
Neutrophils - metabolism
Neutrophils - pathology
Receptors, CCR5 - biosynthesis
Receptors, CCR5 - genetics
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
T-Lymphocytes - pathology
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Summary: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 A 4 , resolvin E1 and protectin D1. Our results suggest that CCR5 + apoptotic leukocytes act as 'terminators' of chemokine signaling during the resolution of inflammation.
ISSN:1529-2908
1529-2916
1365-2567
DOI:10.1038/ni1392