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Regulation of inflammatory responses: possible redox synapse between neutrophils and macrophages.

Authors
Feng-W; Shi-J; Konduru-NV; Bayir-H; Fadeel-B; Kagan-VE
Source
Toxicologist 2010 Mar; 114(1):163
NIOSHTIC No.
20036617
Abstract
The term 'phagocytic synapse' describes the interaction between the professional phagocytic cell and its target via a complex system of receptors, bridging molecules and 'eat me' signals. We hypothesized that the phagocytic synapse is not merely a cell-cell interaction, but also a redox synapse. We predict that the apoptotic neutrophils activate macrophages by PS externalization to utilize them as donors of H2O2 thus satisfying high demands of neutrophils' myeloperoxidase. The provision of H2O2 to the neutrophils may thus lead to the enhancement of myeloperoxidase activity; it may also induce the release of oxygenated free fatty acids or resolvins from apoptotic neutrophils. The local release of oxidized free fatty acids or resolvins may function as a signal to promote the uptake and clearance of apoptotic neutrophils. To test the hypothesis, macrophages differentiated from human monocytes and differentiated neutrophils from PLB-985 cells were used. The extracellular H2O2 levels were monitored by Amplex red assay. Our results show that macrophages have a higher H2O2 generation at resting state than neutrophils, while macrophages produce lower levels of H2O2 than neutrophils upon activation with PMA (10nM). This suggests that macrophages are not likely to be the major providers of H2O2 for activated neutrophils. In cells co-cultured in the presence of H2O2, PMA, or H2O2 plus PMA, the extracellular H2O2 levels were markedly decreased compared to either macrophage or neutrophil incubations alone, suggesting an enhanced consumption of H2O2. This consumption of H2O2 was not diminished by pretreatment of cells with a potent peroxidase inhibitor, NaN3. We conclude that there is a possible synaptic interaction between neutrophils and macrophages in terms of H2O2 consumption.
Keywords
Biological-effects; Cell-biology; Cell-differentiation; Cell-function; Cellular-reactions; Exposure-assessment; Exposure-levels; Exposure-methods; Molecular-biology; Myeloid-tissue; Peroxidases; Phagocytic-activity; Statistical-analysis; Oxygen-transport; Synergism
Publication Date
20100301
Document Type
Abstract
Funding Type
Grant
Fiscal Year
2010
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-008282
Issue of Publication
1
ISSN
1096-6080
Source Name
The Toxicologist. Society of Toxicology 49th Annual Meeting and ToxExpo, March 7-11, 2010, Salt Lake City, Utah
State
WV; UT; PA
Performing Organization
University of Pittsburgh at Pittsburgh
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