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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Decreased CD47 expression during spontaneous apoptosis targets neutrophils for phagocytosis by monocyte-derived
Donald W Lawrence1, Sarah B King, William A Frazier
1Department of Pediatrics, Division of Neonatology, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA.
Background:
Neutrophils (PMN) are the primary leukocyte responders during acute inflammation. After migrating into the tissues, PMN undergo programmed cell death (apoptosis) and are subsequently removed via phagocytosis by resident macrophages during the resolution phase. Efficient phagocytosis of apoptotic neutrophils is necessary for successful resolution. CD47 plays a critical role in mediating the phagocytic response, although its role in the phagocytosis of apoptotic PMN is incompletely understood.
Aims:
In the present study we tested the hypotheses that CD47 modulates the targeting of apoptotic PMN for phagocytosis, and that this process is altered in neonatal PMN.
Study Design:
Adult and neonatal PMN were examined for their expression of CD47. To investigate CD47-mediated functions, apoptotic adult and neonatal PMN were co-cultured with monocyte-derived macrophages (MDM) and the phagocytic index was determined using a flow cytometry-based assay.
Results:
We observed lower basal surface CD47 levels on neonatal vs. adult PMN. In both groups, spontaneous apoptosis led to decreased surface and total cellular CD47 expression. Adult and neonatal MDM ingested apoptotic neonatal target PMN more avidly than apoptotic adult target PMN. Masking of surface CD47 on PMN with a monoclonal antibody enhanced MDM phagocytic activity.
Conclusions:
Our results suggest that age-dependent expression of CD47 on PMN may account for differences in their ingestion by macrophages and in the resolution of inflammation.
Insights
Neonatal neutrophils show lower CD47 expression, leading to enhanced macrophage phagocytosis compared to adult neutrophils. This age-dependent CD47 expression impacts inflammatory resolution.
Area of Science:
- Immunology
- Cell Biology
- Neonatal Research
Background:
- Neutrophils are key in acute inflammation and are cleared by macrophages after apoptosis.
- Efficient clearance of apoptotic neutrophils is crucial for resolving inflammation.
- CD47's role in apoptotic neutrophil phagocytosis is not fully understood.
Purpose of the Study:
- To investigate if CD47 influences the targeting of apoptotic neutrophils for phagocytosis.
- To determine if this CD47-mediated process differs between adult and neonatal neutrophils.
Main Methods:
- Compared CD47 expression on adult and neonatal neutrophils.
- Co-cultured apoptotic neutrophils with macrophages to assess phagocytosis using flow cytometry.
- Investigated CD47 function by blocking its surface expression.
Main Results:
- Neonatal neutrophils had lower basal CD47 levels than adult neutrophils.
- Apoptotic neutrophils showed reduced CD47 expression.
- Macrophages avidly ingested apoptotic neonatal neutrophils over adult neutrophils.
- Blocking CD47 on neutrophils enhanced macrophage phagocytosis.
Conclusions:
- Age-dependent CD47 expression on neutrophils influences their phagocytosis by macrophages.
- Differences in CD47 expression may affect inflammatory resolution in neonates versus adults.
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