The glycosylphosphatidylinositol‐linked Fcγ receptor III represents the dominant receptor structure for immune complex activation of neutrophils

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Abstract
Polymorphonuclear neutrophils (PMN) express constitutively two low-affinity Fcγ receptors, FcγRII and FcγRIII. FcγRII is a transmembrane molecule, and FcγRIII is linked via a glycosylphosphatidylinositol (GPI) anchor to the membrane. The role of each of these receptors in activation of PMN is still unclear. We used specific cross-linking of FcγRII via Fab fragments of IV.3 (anti-FcγRII, CDw32) and of FcγRIII using F(ab')2 fragments of 3G8 (anti-FcγRIII, CD16) to activate PMN. Stimulation of FcγRIII was significantly more effective in inducing a respiratory burst than cross-linking of FcγRII. A synergistic effect was observed after simultaneous activation of FcγRIII. We could demonstrate that both FcγR mobilize calcium as intracellular signal in spite of their different membrane linkage. The kinetic of calcium mobilization after FcγR stimulation is delayed in comparison to formyl-methionyl-leucyl-phenylalanine activation. In addition FcγR-induced increase of cytoplasmic calcium is pertussis toxin insensitive. When monoclonal IgG1χ complexes were used for stimulation calcium mobilization and hydrogen peroxide (H2O2) production could also be demonstrated. Inhibition studies of this activation using monoclonal antibodies suggested that this immune complex activation was predominantly mediated via FcγRIII. Only in FcγRIII-deficient PMN from paroxysmal nocturnal hemoglobinuria patients could a decreased H2O2 production be demonstrated to be FcγRII dependent. In normal PMN the GPI-anchored FcγRIII structure is the predominant receptor.

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