Phagocytosis of senescent neutrophils by human monocyte-derived macrophages and rabbit inflammatory macrophages

From the time that the inflammatory reaction was first characterized by its cardinal signs of color, rubor, tumor, et dolor, until the studies on phagocytosis by Metchnikoff, it was considered that this reaction by the organism was detrimental to its well being. Metchnikoff (1), however, saw the process of inflammation as a " . . . salutary reaction against some injurious influence." He stated (1) that there were " . . . two classes of phenomena in inflammation; first, inflammation properly so-called, i.e., the lesion of the vessel walls and other disturbances brought about by the irritating cause; second, repair, consisting in the regeneration of the missing tissues and in the formation of a scar." It is the second process, that of repair or resolution of the inflammatory response, that was the impetus for this investigation. The ingestion of phagocytes by other phagocytes was first described by Metchnikoff. In studies in the fins of tadpoles (2), he noted that phagocytes that had perished at the site of inflammation were "englobed by other phagocytes." Metchnikoff also described this phenomenon in an inflammatory response to streptococci: "the streptococci are englobed only by polynuclear leukocytes, and are never taken up by the macrophages, which, however, carry out the entire work of absorption, and even englobe the microphages, many of which perish in the struggle with the microbes and have to be themselves absorbed" (3). The ingestion of effete neutrophils by incoming macrophages is probably one of several mechanisms that are operable in the final stages of an inflammatory reaction. Since Metchnikoff, however, other descriptions of the ingestion of neutrophils by macrophages have come mainly from the clinical literature. This phenomenon has been described in various disease states, such as in macrophage granulomas in the liver after infection with ornithosis virus (4), in marrow macrophages in childhood chronic benign neutropenia (5), in connective t i s~e macrophages in histiocytic medullary reticulosis (6), in splenic macrophages i~ti thrombotic thrombocytopenic purpura (7), and in splenic Reed-Sternbet'g cells in Hodgkin's disease (8). Heifets et al. (9) repored that resident mouse peritoneal macrophages can ingest human neutrophils or neutrophil granules that provided the macrophages with neutrophil peroxidase that was functional in iodination when the macrophages phagocytized opsonized zymosan. In uhrastructural studies, a few guinea pig perito-