NA1/NA2 Antisera Inhibit FcγRI- but Not FcγRII- Mediated Phagocytosis

Background and Objectives: Alloantibodies against the granulocyte-specific NA antigens play an important role in alloimmune neonatal neutropenia. As the NA system is located on the FcγRIIIb, the influence of NA-specific antibodies on granulocyte function is of special interest. Materials and Methods: We tested alloantisera specific for NA1 and NA2 for their ability to influence FcγR-mediated phagocytosis of polymorphonuclear neutrophils by use of different FcγR-specific targets. Red blood cells coated with human IgG anti-D served as specific targets for FcγRI-mediated phagocytosis while mouse IgG1 anti-glycophorin A was used to coat red blood cells (RBCs) to obtain FcγRII specific targets. To test for a hypothetical induction of phagocytosis by FcγRIIIb we used D-- RBCs coated with human monoclonal anti-D as target cells for unprimed neutrophils. Results: Granulocyte phagocytosis was directly induced by FcγRI and FcγRII but not by FcγRIIIb. NA1 alloantisera significantly inhibited FcγRI-mediated phagocytosis of IFN-γ-stimulated neutrophils if the corresponding antigen was expressed. Conversely, NA2 alloantisera inhibited FcγRI-mediated phagocytosis in NA2-positive individuals. There was no effect of NA1- and NA2-specific alloantibodies on FcγRII-mediated phagocytosis. Conclusion: NA-specific alloantisera inhibit the FcγRI-induced phagocytosis in primed neutrophils, but they do not significantly inhibit their FcγRIIa-specific phagocytosis of mIgG1-coated RBCs.