Enhanced Phagocytosis in Neonatal Monocyte-Derived Macrophages is Associated with Impaired SHP-1 Signaling

Abstract

Resident macrophages represent a first line of defense through the ingestion of microbial pathogens. Phagocytosis mediated by immunoglobulin-binding Fc receptors is a complex series of events involving tyrosine phosphorylation and dephosphorylation. In the present study we determined that the phagocytic capacity of neonatal monocyte-derived macrophage (MDM) was enhanced in comparison to adult MDM. Cross-linking of surface FcγRIIa receptors enhanced tyrosine phosphorylation of several proteins in both groups, followed by a reduction in tyrosine phosphorylation in adult but not neonatal MDM. Expression of the tyrosine phosphatase SHP-1 was similar in neonatal and adult MDM; however, baseline SHP-1 activity levels were diminished in neonatal MDM. Cross-linking of FcγRIIa receptors induced a greater increase in SHP-1 activity in adult MDM vs. neonatal MDM. The cytoplasmic adapter protein Cbl is a SHP-1 ligand and negatively affects phagocytosis. As determined by co-immunoprecipitation assays, SHP-1 and Cbl did not associate to the same extent in neonatal as compared to adult MDM. Our data suggest that the enhanced phagocytic capacity of neonatal MDM is associated with decreased SHP-1 activity and alteration of downstream signaling pathways.

• Macrophage
• Phagocytosis
• Fc receptor
• SHP-1

ACKNOWLEDGMENTS

The authors thank our research nurse Amy Cooper, RN, and the Labor and Delivery staff and obstetricians of SSM St. Mary’s Medical Center for their gracious assistance with the acquisition of cord blood samples.

Declaration of interest: The authors declare no conflicts of interest to disclose. This work was funded in part by NIH grant HD47401 (J.M.K.), and a grant from the Fleur De Lis Foundation, Cardinal Glennon Children’s Medical Center (D.W.L.).