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Phagocytosis of apoptotic cells by neutrophil granulocytes: diminished proinflammatory neutrophil functions in the presence of apoptotic cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Esmann, Lars Klinger, Matthias Möller, Sonja Laskay, Tamás Bussmeyer, Uta Idel, Christian Sarkar, Arup Behnen, Martina Solbach, Werner Köhl, Jörg Van Zandbergen, Ger Hellberg, Lars
Description	Country affiliation: Germany Author Affiliation: Esmann L ( Institute for Medical Microbiology and Hygiene, University of Lübeck, Lübeck, Germany.)
Abstract	Neutrophil granulocytes are rapidly recruited from the bloodstream to the site of acute inflammation where they die in large numbers. Because release of toxic substances from dead neutrophils can propagate the inflammatory response leading to tissue destruction, clearance of dying inflammatory neutrophils has a critical function in the resolution of the inflammatory response. Apoptotic neutrophils are phagocytosed primarily by macrophages, provided these cells are present in adequate numbers. However, macrophages are rare at sites of acute inflammation, whereas the number of neutrophils can be extremely high. In the current study, in vitro experiments with human neutrophils were carried out to investigate whether neutrophils can ingest apoptotic neutrophils. We show that naïve granulocytes isolated from venous blood have a limited capacity to phagocytose apoptotic cells. However, exposure to activating stimuli such as LPS, GM-CSF and/or IFN-gamma results in enhanced phagocytosis of apoptotic cells. The efficient uptake of apoptotic cells by neutrophils was found to depend on the presence of heat labile serum factors. Importantly, the contact to or uptake of apoptotic cells inhibited neutrophil functions such as respiratory burst and the release of the proinflammatory cytokines TNF-alpha and interferon-inducible protein-10. Contact to apoptotic cells, however, induced the secretion of IL-8 and growth-related oncogene-alpha, which was independent of NF-kappaB and p38 MAPK but involved C5a and the ERK1/2 pathway. The data suggest that activated neutrophils participate in the clearance of apoptotic cells. In addition, because apoptotic cells inhibit proinflammatory functions of neutrophils, uptake of apoptotic cells by neutrophils contributes to the resolution of inflammation.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	1
Volume Number	184
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2010-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Apoptosis Immunology Inflammation Neutrophils Phagocytosis Cells, Cultured Cytokines Biosynthesis Respiratory Burst Signal Transduction Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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