NA1/NA2 antisera inhibit Fc gamma RI- but not Fc gamma RII-mediated phagocytosis

Background and Objectives: Alloantibodies against the granulocyte-specific NA antigens play an important role in alloimmune neonatal neutropenia. As t he NA system is located on the Fc gamma RIIIb, the influence of NA-specific antibodies on granulocyte function is of special interest. Materials and M ethods: We tested alloantisera specific for NA1 and NA2 for their ability t o influence Fc gamma R-mediated phagocytosis of polymorphonuclear neutrophi ls by use of different Fc gamma R-specific targets. Red blood cells coated with human IgG anti-D served as specific targets for Fc gamma RI-mediated p hagocytosis while mouse IgG1 anti-glycophorin A was used to coat red blood cells (RBCs) to obtain Fc gamma RII specific targets. To test for a hypothe tical induction of phagocytosis by Fc gamma RIIIb we used D- RBCs coated wi th human monoclonal anti-D as target cells for unprimed neutrophils. Result s: Granulocyte phagocytosis was directly induced by Fc gamma RI and Fc gamm a RII but not by Fc gamma RIIIb. NA1 alloantisera significantly inhibited F c gamma RT-mediated phagocytosis of IFN-gamma-stimulated neutrophils if the corresponding antigen was expressed. Conversely, NA2 alloantisera inhibite d Fc gamma RI-mediated phagocytosis in NA2-positive individuals. There was no effect of NA1- and NA2-specific alloantibodies on Fc gamma RII-mediated phagocytosis. Conclusion: NA-specific alloantisera inhibit the Fc gamma RI- induced phagocytosis in primed neutrophils, but they do not significantly i nhibit their Fc gamma RIIa-specific phagocytosis of mIgG1-coated RBCs.