To assess key events in the resolution of acute inflammation, Serhan and colleagues studied mouse peritonitis that was induced by injection of zymosan A (a cell-wall component of yeast). The authors noted that, 12 hours after the induction of peritonitis, peritoneal exudate from mice that were deficient in CC-chemokine receptor 5 (CCR5) contained greater amounts of the CCR5 ligands CC-chemokine ligand 3 (CCL3) and CCL5 than did exudate from wild-type mice. By contrast, CCR5 deficiency did not prevent the reduction in levels of the pro-inflammatory chemokine CXC-chemokine ligand 12 (CXCL12; which is not a ligand for CCR5) that normally occurs 12 hours after the induction of inflammation. These findings indicated that CCR5 might be involved in the clearance of its pro-inflammatory chemokine ligands during the resolution of inflammation.
Next, the authors asked whether neutrophils that are undergoing apoptosis in the inflamed peritoneal cavity might be involved in the clearance of CCR5 ligands. To address this, the authors transferred apoptotic neutrophils from wild-type or CCR5-deficient mice into the peritoneal cavities of CCR5-deficient mice with peritonitis, then (1 hour later) measured the chemokine levels in the peritoneal exudate. Indeed, the peritoneal exudate of mice that had received wild-type apoptotic neutrophils contained less CCL3 and CCL5, as well as slightly less of the pro-inflammatory cytokine tumour-necrosis factor, than did the exudate of mice that had received CCR5-deficient cells. Moreover, that apoptotic neutrophils have a role in this process was supported by the observation that these cells expressed large amounts of CCR5, particularly at late stages of apoptosis (as determined by positive staining with propidium iodide).
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