TY - JOUR
T1 - Phagocytosis of apoptotic cells by neutrophil granulocytes: Diminished proinflammatory neutrophil functions in the presence of apoptotic cells
AU - Esmann, Lars
AU - Idel, Christian
AU - Sarkar, Arup
AU - Hellberg, Lars
AU - Behnen, Martina
AU - Möller, Sonja
AU - Van Zandbergen, Ger
AU - Klinger, Matthias
AU - Köhl, Jörg
AU - Bussmeyer, Uta
AU - Solbach, Werner
AU - Laskay, Tamás
PY - 2010/1/1
Y1 - 2010/1/1
N2 - Neutrophil granulocytes are rapidly recruited fromthe bloodstream to the site of acute inflammation where they die in large numbers. Because release of toxic substances fromdeadneutrophilscan propagate theinflammatory response leadingto tissue destruction, clearance of dying inflammatory neutrophils hasa critical function in the resolutionof 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, invitro experiments with human neutrophils were carried out to investigate whether neutrophils can ingest apoptotic neutrophils. We show that naïve granulocytes isolated fromvenous blood have a limited capacity to phagocytose apoptotic cells. However, exposure to activating stimuli such as LPS, GM-CSF and/or IFN-γ 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-α and interferon-inducible protein-10. Contact to apoptotic cells, however, induced the secretion of IL-8 and growth-related oncogene-α, which was independent of NF-κB 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.
AB - Neutrophil granulocytes are rapidly recruited fromthe bloodstream to the site of acute inflammation where they die in large numbers. Because release of toxic substances fromdeadneutrophilscan propagate theinflammatory response leadingto tissue destruction, clearance of dying inflammatory neutrophils hasa critical function in the resolutionof 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, invitro experiments with human neutrophils were carried out to investigate whether neutrophils can ingest apoptotic neutrophils. We show that naïve granulocytes isolated fromvenous blood have a limited capacity to phagocytose apoptotic cells. However, exposure to activating stimuli such as LPS, GM-CSF and/or IFN-γ 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-α and interferon-inducible protein-10. Contact to apoptotic cells, however, induced the secretion of IL-8 and growth-related oncogene-α, which was independent of NF-κB 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.
UR - http://www.scopus.com/inward/record.url?scp=73949115341&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.0900564
DO - 10.4049/jimmunol.0900564
M3 - Journal articles
C2 - 19949068
AN - SCOPUS:73949115341
SN - 0022-1767
VL - 184
SP - 391
EP - 400
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -