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Phagocytosis of apoptotic neutrophils does not induce macrophage release of thromboxane B 2
Author(s) -
Meagher Laura C.,
Savill John S.,
Baker Amanda,
Fuller Richard W.,
Haslett Christopher
Publication year - 1992
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.52.3.269
Subject(s) - phagocytosis , zymosan , proinflammatory cytokine , biology , macrophage , apoptosis , immunology , phagocyte , efferocytosis , inflammation , microbiology and biotechnology , biochemistry , in vitro
Senescent human neutrophils undergo programmed cell death (apoptosis), leading to their recognition and phagocytosis by mature macrophages. At inflamed sites in vivo these processes may represent a neutrophil removal mechanism with the potential to limit the histotoxic capacity of these cells. Phagocytosis can provoke marked proinflammatory responses by macrophages. A macrophage proinflammatory response to the ingestion of apoptotic neutrophils would limit the efficacy of this nautrophil removal mechanism as a component of inflammatory resolution. In the present study we examined two macrophage proinflammatory responses; secretion of the granule enzyme N ‐acetyl‐β‐d‐glucosaminidase (NAG) and release of the membrane lipid‐derived inflammatory mediator thromboxane A 2 (TxA 2 , measured as TxB 2 ). By contrast with the marked release of NAG and TxB 2 elicited by phagocytosis of control particles (opsonised zymosan and immunoglobulin G–coated erythrocytes), macrophage ingestion of apoptotic neutrophils resulted in minimal release of NAG and no release of TxB 2 ; indeed, there was a small depression of TxB 2 release that was not due to a toxic effect of neutrophil uptake because macrophages ingesting apoptotic neutrophils retained marked TxB 2 responses to subsequent stimulation with opsonised zymosan. Furthermore, there was significant TxB 2 release in response to macrophage phagocytosis of apoptotic neutrophils that had been coated with opsonic serum, demonstrating that the lack of macrophage response was determined by the mechanism of recognition rather than the properties of the apoptotic particle itself. These observations are consistent with the hypothesis that macrophage clearance of senscent neutrophils undergoing apoptosis is an injury‐limiting mechanism that favors resolution rather than persistence of the inflammatory response and are consistent with observations that the waves of apoptotic cell removal seen in embryological removal and thymic involution do not trigger an inflammatory response.