Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expression

Amiram Ariel; Gabrielle Fredman; Yee Ping Sun; Alpdogan Kantarci; Thomas E. Van Dyke; Andrew D. Luster; Charles N. Serhan

doi:10.1038/ni1392

Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expression

Amiram Ariel, Gabrielle Fredman, Yee Ping Sun, Alpdogan Kantarci, Thomas E. Van Dyke, Andrew D. Luster, Charles N. Serhan

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	1209-1216
Number of pages	8
Journal	Nature Immunology
Volume	7
Issue number	11
DOIs	https://doi.org/10.1038/ni1392
State	Published - Nov 2006
Externally published	Yes

Bibliographical note

Funding 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
Immunology

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title = "Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expression",

abstract = "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.",

author = "Amiram Ariel and Gabrielle Fredman and Sun, {Yee Ping} and Alpdogan Kantarci and {Van Dyke}, {Thomas E.} and Luster, {Andrew D.} and Serhan, {Charles N.}",

note = "Funding 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.).",

year = "2006",

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doi = "10.1038/ni1392",

language = "English",

volume = "7",

pages = "1209--1216",

journal = "Nature Immunology",

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T1 - Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expression

AU - Ariel, Amiram

AU - Fredman, Gabrielle

AU - Sun, Yee Ping

AU - Kantarci, Alpdogan

AU - Van Dyke, Thomas E.

AU - Luster, Andrew D.

AU - Serhan, Charles N.

N1 - Funding 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.).

PY - 2006/11

Y1 - 2006/11

N2 - 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.

AB - 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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JO - Nature Immunology

JF - Nature Immunology

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ER -

Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expression

Abstract

Bibliographical note

ASJC Scopus subject areas

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