IN-VIVO FATE OF THE INFLAMMATORY MACROPHAGE DURING THE RESOLUTION OF INFLAMMATION - INFLAMMATORY MACROPHAGES DO NOT DIE LOCALLY, BUT EMIGRATE TO THE DRAINING LYMPH-NODES

The resolution of acute inflammation requires bulk clearance of extrav asated inflammatory cells in an ordered manner, Neutrophils undergo ap optosis and are ingested by macrophages (M phi) via a novel recognitio n mechanism that fails to provoke proinflammatory responses, Thereafte r, the fate of inflammatory M phi themselves remains unclear, We inves tigated this in vivo, developing a semiallogeneic adoptive transfer sy stem to track the fate of inflammatory M phi in a murine model of reso lving peritonitis, Fluorescently labeled M phi from H-2(k/d) mice were transferred into the peritoneal cavity of H-2(k) mice at the same sta ge of resolving inflammation as the donor mice, Dual color flow cytome try permitted discrimination among donor cells, recipient cells, and d onor cells that had been phagocytosed by recipient M phi. Despite the absence of significant local phagocytosis, the number of transferred M phi free in the peritoneum of recipient mice declined rapidly, being undetectable by 96 h, These data suggest that inflammatory M phi norma lly emigrate rapidly from the peritoneal cavity during the resolution of inflammation, contrasting with resident M phi, which persist in the noninflamed peritoneum for weeks, Accordingly, labeled non-phagocytos ed cells were detected in the draining lymph nodes, but not in a varie ty of other tissues, Thus, unlike the polymorphonuclear leukocyte, whi ch dies by apoptosis and is ingested by M phi, the inflammatory M phi itself does not die locally, Having performed its acute inflammatory a nd scavenging roles, it emigrates in a nonrandom fashion to the draini ng lymph node, where it may play an important part in the presentation of Ags from the inflamed site.