CCL5 Promotes Resolution-Phase Macrophage Reprogramming in Concert with the Atypical Chemokine Receptor D6 and Apoptotic Polymorphonuclear Cells
| Autor: | Miran Aswad, Amiram Ariel, Simaan Assi, Sagie Schif-Zuck |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Chemokine Neutrophils Immunology Apoptosis Inflammation Receptors CCR10 Peritonitis CCL5 Proinflammatory cytokine Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Immunology and Allergy Macrophage Chemokine CCL5 biology Macrophages Zymosan hemic and immune systems Cell biology CXCL2 030104 developmental biology Gene Expression Regulation biology.protein medicine.symptom Reprogramming Ex vivo Protein Binding 030215 immunology |
| Zdroj: | The Journal of Immunology. 199:1393-1404 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | The engulfment of apoptotic polymorphonuclear cells (PMN) during the resolution of inflammation leads to macrophage reprogramming culminating in reduced proinflammatory and increased anti-inflammatory mediator secretion. The atypical chemokine receptor D6/ACKR2 is expressed on apoptotic PMN and plays an important role in regulating macrophage properties during and after engulfment. In this study, we found that the inflammatory chemokine CCL5 is mostly retained (75%) during the resolution of zymosan A peritonitis in mice. Moreover, this chemokine is secreted by resolution-phase macrophages (2.5 ng/ml) and promotes their reprogramming in vivo in D6+/+ mice (2-fold increase in IL-10/IL-12 ratio) but not their D6−/− counterparts. In addition, CCL5 enhanced macrophage reprogramming ex vivo exclusively when bound to D6+/+ apoptotic PMN. Signaling through p38MAPK and JNK in reprogrammed macrophages was enhanced by CCL5-bound apoptotic PMN (3.6–4 fold) in a D6-dependent manner, and was essential for reprogramming. Thus, CCL5 exerts a novel proresolving role on macrophages when acting in concert with apoptotic PMN-expressed D6. |
| Databáze: | OpenAIRE |
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