Key Points
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Neutrophils, monocytes and macrophages arise from common precursors, explaining much of their functional and phenotypical overlap. However, these cells also have complementary functions during the onset and resolution of inflammation.
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After sensing alarming stimuli, tissue-resident macrophages and sentinel monocytes promote an inflammatory response through release of chemokines (such as CXC-chemokine ligand 1 (CXCL1), CXCL2 and CXCL8) and pro-inflammatory lipid mediators (such as leukotrienes).
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Neutrophils are the 'advance guard' for inflammatory monocytes. Neutrophil-derived granule proteins (such as azurocidin and LL-37) and neutrophil protease-driven alterations of the local chemokine network promote rapid infiltration of monocytes to sites of inflammation.
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Monocyte-derived macrophages and apoptotic neutrophils abrogate further neutrophil influx by secreting anti-inflammatory lipid-mediators (such as lipoxins) or inactivating chemokines.
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Neutrophils undergoing apoptosis release signals that attract monocytes to the site of inflammation. Phagocytic clearance of apoptotic neutrophils reprogrammes monocyte-derived macrophages from a pro-inflammatory to an anti-inflammatory phenotype.
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The interplay between phagocyte subsets during the onset and resolution of inflammation could be targeted for therapeutic purposes. Potential targets for intervention include neutrophil-derived granule proteins, neutrophil apoptosis, or chemokines and lipid-mediators released from different phagocyte subsets.
Abstract
Neutrophils, monocytes and macrophages are closely related phagocytic cells that cooperate during the onset, progression and resolution of inflammation. This Review highlights the mechanisms involved in the intimate partnership of phagocytes during each progressive phase of the inflammatory response. We describe how tissue-resident macrophages recognize tissue damage to promote the recruitment of neutrophils and the mechanisms by which infiltrating neutrophils can then promote monocyte recruitment. Furthermore, we discuss the phagocyte-derived signals that abrogate neutrophil recruitment and how the uptake of apoptotic neutrophils by macrophages leads to termination of the inflammatory response. Finally, we highlight the potential therapeutic relevance of these interactions.
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Acknowledgements
The authors' research is supported by the Deutsche Forschungsgemeinschaft (SO876/3-1, SO876/4-1 and FOR809), the German Heart Foundation and German Foundation of Heart Research, the START programme within the Faculty of Medicine at the RWTH Aachen University, the Swedish Research Council, the Swedish Heart-Lung Foundation, Swedish Foundation for Strategic Research and Karolinska Institutet.
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Glossary
- Secretagogue
-
A substance that causes another substance to be secreted.
- Pertussis toxin
-
Pertussis toxin blocks Gαi-coupled receptor signalling (including chemokine-receptor signalling) by catalysing ADP ribosylation of the Gαi subunit.
- ELR motif
-
A conserved glutamatic acid–leucine–arginine (ELR) sequence found in CXC-chemokines immediately preceding the first cysteine residue near the amino-terminal end. The motif is crucial for receptor ligation and the chemotactic activity of neutrophils.
- 'Find me' signal
-
A signal emitted by dying cells to promote the recruitment of scavenger cells that clear the apoptotic cell body.
- 'Eat me' signal
-
A signal emitted by dying cells to facilitate their recognition and phagocytosis.
- Electrotaxis
-
Movement of an organism or a cell in response to stimulation by electric charges.
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Soehnlein, O., Lindbom, L. Phagocyte partnership during the onset and resolution of inflammation. Nat Rev Immunol 10, 427–439 (2010). https://doi.org/10.1038/nri2779
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DOI: https://doi.org/10.1038/nri2779
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