Abstract
Phagocytosis of apoptotic cells, e.g., neutrophils, by monocytes is essential for resolution of inflammation. Delayed removal leads to secondary necrosis, perpetuating inflammation, and tissue destruction. Common histologic features in neonatal chronic inflammatory disorders are an accumulation of apoptotic cells in inflamed tissues. We hypothesized that apoptotic cell removal by monocytes is compromised in newborns. PKH-26 labeled autologous or allogeneic apoptotic neutrophils were fed to monocytes of adult donors (PBMO) and cord blood (CBMO), and phagocytic activity was analyzed by flow cytometry and confocal microscopy. Relative mRNA-expression levels of 21 surface receptors and bridging molecules relevant for apoptotic cell removal were measured, as was postphagocytic IL-8 production upon LPS-stimulation. Compared with PBMO, CBMO exhibited a significantly diminished phagocytotic competence for autologous and allogeneic apoptotic neutrophils. mRNA-expression levels of milk fat globule-EGF factor 8 and T cell immunoglobulin- and mucin-domain-containing molecule, two crucial members of the phagocytic synapse of apoptotic cell removal, were reduced in CBMO. In PBMO, interaction with autologous apoptotic neutrophils reduced LPS-induced IL-8 production whereas it was enhanced in CBMO. Our data suggest a specific defect in CBMO during clearance of apoptotic neutrophils resulting in impaired anti-inflammatory capacity.
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Abbreviations
- CBMC:
-
cord blood mononuclear cells
- CBMO:
-
cord blood monocytes
- MFG-E8:
-
milk fat globule-EGF factor 8
- PBMC:
-
peripheral blood mononuclear cells of adult blood
- PBMO:
-
peripheral blood monocytes of adult blood
- TIM4:
-
T-cell immunoglobulin- and mucin-domain-containing molecule
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Acknowledgements
We thank Andrea Schäfer, Department of Medical Microbiology, for help with confocal microscopy and Derek Stebbens for carefully reading the manuscript.
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Supported by the FORTUNE-program, grant number 1386-0-0, of the Medical Faculty of the University of Tuebingen (C.G.) and Deutsche Forschungsgemeinschaft SFB 685 (K.L.).
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Gille, C., Steffen, F., Lauber, K. et al. Clearance of Apoptotic Neutrophils Is Diminished in Cord Blood Monocytes and Does Not Lead to Reduced IL-8 Production. Pediatr Res 66, 507–512 (2009). https://doi.org/10.1203/PDR.0b013e3181b9b470
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DOI: https://doi.org/10.1203/PDR.0b013e3181b9b470
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