title: 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.
authors.affiliation: Department of Pediatrics, Division of Neonatology, Saint Louis University School of Medicine, Saint Louis, MO, USA.
authors.forename: Donald W
authors.initials: DW
authors.lastname: Lawrence
authors.forename: Joyce M
authors.initials: JM
authors.lastname: Koenig
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D004789:Enzyme Activation; D006801:Humans; D007231:Infant, Newborn; D008264:Macrophages / Q000276:immunology*; D010587:Phagocytosis; D010766:Phosphorylation; D021381:Protein Transport; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism*; D011940:Receptor Aggregation; D017452:Receptors, IgG / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C445323:FCGR2A protein, human; D017452:Receptors, IgG; D050721:Proto-Oncogene Proteins c-cbl; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C067419:CBL protein, human