Decreased CD47 expression during spontaneous apoptosis targets neutrophils for phagocytosis by monocyte-derived macrophages

Abstract

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.