This very act of cell death—notably of neutrophils and T cells—is one way of actively resolving an inflammatory event. But the signals that first drew immune cells to the site of inflammation also need to be destroyed: chemicals via enzymatic degradation and proteins and peptides by other means. Now, the Boston team shows that some of these chemokine proteins are mopped up by apoptotic cells. These dying cells turn up expression of their CCR5 chemokine receptors even as the cells are about to be engulfed by macrophages.
CCR5 is important because it binds several key chemokines—“the lion's share of the chemokines at a site of inflammation,” says Serhan. “So you need a good mechanism to explain their clearance.”
Late apoptotic cells had higher CCR5 staining; this was reduced by a proinflammatory cytokine but increased by proresolution mediators. The result was more chemokine binding to late apoptotic cells. If CCR5 was knocked out or antagonized, however, fluid from resolving infections had higher chemokine levels.
Thus it appears that the dying cells are mopping up chemokines and taking them to the grave. “It sounds almost too simple,” says Serhan, but he doesn't think this is his “Mission Accomplished.” Rather it is a reminder, he says, that “when cells go through apoptosis they don't stop signaling.”