Macrophages bind to all neutrophils at 20°C, but viable ones escape at 37°C.

Brown/Macmillan

When macrophages perform their search-and-destroy missions, it is not simply up to apoptotic cells to flag down their destroyers. New results from Simon Brown (University of Edinburgh, Edinburgh, UK) and colleagues reveal that viable cells must actively avoid engulfment by phagocytes. A single cell adhesion molecule, CD31, can lead to either engulfment or escape.Brown and his colleagues found CD31 by purifying proteins involved in tethering of cells to macrophages at low temperatures, when phagocytosis and cytoskeletal rearrangements were inhibited. Both viable and apoptotic leukocytes bound to macrophages through homophilic CD31 interactions. At 37°C, however, this interaction was transient for viable leukocytes. The cytoplasmic portion of CD31 imparted these cells with the ability to avoid destruction by actively promoting detachment from the macrophages. Apopotic cells had somehow lost this capability.

“‘Eat-me signals’ are what are usually looked for, but we found ‘don’t-eat-me signals' instead,” says Brown. “It would seem more efficient for an apoptotic cell to lose a signaling ability than gain one.” In this way, and by ligating self-recognition receptors, macrophages can determine whether a cell has lost its ability to respond to external signals and is thus ready for disposal. Whether viable cells actively escape from macrophages either by activating motility machinery (as happens upon CD31 ligation between leukocytes and endothelial cells) or by inhibiting subsequent interactions between the target and the macrophage is the focus of continuing studies. ▪

Reference:

Brown, S., et al.
2002
.
Nature.
418
:
200
–203.