Abstract |
The resolution of acute inflammation is hallmarked by the apoptotic death of inflammatory polymorphonuclear (PMN) cells, followed by their clearance by macrophages. In turn, resolution-phase macrophages exert reduced proinflammatory cytokine production, termed immune silencing. In this study, we found that the atypical chemokine receptor D6 plays an important and chemokine scavenging-independent role in promoting macrophage-mediated resolution. D6(-/-) mice displayed increased numbers of macrophages (2.2-fold increase), but not neutrophils, in their peritonea during the resolution of murine zymosan A-initiated peritonitis, in comparison to D6(+/+) animals. Moreover, D6-deficient macrophages engulfed higher numbers of apoptotic PMN cells in vivo (1.6-fold increase), and secreted higher amounts of TNF-α, CCL3, and CCL5 ex vivo than their wild-type (WT) counterparts. In addition, D6 was found to be expressed on apoptotic neutrophils from healthy humans and rodents. Moreover, the immune silencing of LPS-stimulated macrophages following their incubation with senescent PMN cells ex vivo (in terms of TNF-α, IL-1β, and CCL5 secretion) was diminished (50-65% decrease) when D6(-/-) PMN cells were applied. Accordingly, the adhesive responses induced by macrophage interactions with senescent PMN cells were reduced with D6-deficient PMN cells. Thus, our results indicate a novel mode of action for D6 during the resolution of inflammation that is instrumental to the shaping of resolving macrophage phenotypes and the completion of resolution.
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Authors | Ester Pashover-Schallinger, Miran Aswad, Sagie Schif-Zuck, Haim Shapiro, Pierre Singer, Amiram Ariel |
Journal | FASEB journal : official publication of the Federation of American Societies for Experimental Biology
(FASEB J)
Vol. 26
Issue 9
Pg. 3891-900
(Sep 2012)
ISSN: 1530-6860 [Electronic] United States |
PMID | 22651933
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cytokines
- Receptors, CCR10
- chemokine receptor D6
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Topics |
- Animals
- Apoptosis
- Cytokines
(metabolism)
- Enzyme-Linked Immunosorbent Assay
- Macrophages
(immunology, metabolism)
- Mice
- Mice, Knockout
- Neutrophils
(cytology, metabolism)
- Peritonitis
(metabolism, physiopathology)
- Receptors, CCR10
(genetics, physiology)
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