| First Author | Pashover-Schallinger E | Year | 2012 |
| Journal | FASEB J | Volume | 26 |
| Issue | 9 | Pages | 3891-900 |
| PubMed ID | 22651933 | Mgi Jnum | J:187443 |
| Mgi Id | MGI:5437145 | Doi | 10.1096/fj.11-194894 |
| Citation | Pashover-Schallinger E, et al. (2012) The atypical chemokine receptor D6 controls macrophage efferocytosis and cytokine secretion during the resolution of inflammation. FASEB J 26(9):3891-900 |
| abstractText | 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-alpha, 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-alpha, IL-1beta, 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.-Pashover-Schallinger, E., Aswad, M., Schif-Zuck, S., Shapiro, H., Singer, P., Ariel, A. The atypical chemokine receptor D6 controls macrophage efferocytosis and cytokine secretion during the resolution of inflammation. |
