The first attackers arriving at the scene of an infection in the abdominal cavity are neutrophils with a later peak in monocytes and macrophages. As the infection wanes, the neutrophils apoptose and are engulfed by macrophages. “The foot soldiers all shrivel up and die,” says Bellingan, “but no one really addressed how these other guys [the macrophages] would be cleared.”
The London team found that the macrophages departed through the lymphatics, with the activated inflammatory macrophages (rather than the resident macrophages) being cleared preferentially. The activated macrophages adhered only to areas overlying the lymphatics, and both the adhesion and the exit were inhibited by agents that block β1-integrin-dependent adhesion.
Similar inhibitors have been used preclinically to slow influx of leukocytes. But Bellingan points out that such agents, if administered too late, may prolong inflammation by blocking macrophage exit. As to what triggers the exit, Bellingan guesses that ingestion of either apoptotic neutrophils or other targets may cause a switch in the activity of macrophage adhesion molecules, thus initiating the exit procedure. ▪