FUNCTIONAL-CAPACITY OF FC-GAMMA RECEPTOR-III (CD16) ON HUMAN NEUTROPHILS

Receptors for the Fc region of immunoglobulin G (IgG) are a structurally diverse group of molecules. Within the three FcgammaR families (FcgammaRI, FcgammaRII and FcgammaRIII), the presence of distinct genes and alternative splicing variants leads to a variety of receptor isoforms that are most strikingly different in the transmembrane and intracellular regions. An obvious example of structural variation in the transmembrane and cytoplasmic domains is observed in the FcgammaRIII family. FcgammaRIIIB, which is nearly identical to FcgammaRIIIA in the extracellular domains, lacks both transmembrane and cytoplasmic protein domains and is anchored to the cell through a glycosyl phosphatidylinositol anchor. Analysis of FcgammaRIII function presents a considerable challenge in understanding the role of different FcgammaR receptors in polymorphonuclear neutrophil (PMN) function. While one hypothesis for the role of FcgammaRIII in FcgammaR-dependent PMN effector functions is that FcgammaRIII serves as a binding molecule which focuses the IgG ligand for more efficient recognition and intracellular signaling by FcgammaRII, recent observations from a number of laboratories suggest that FcgammaRIII on PMN can transduce signals across the membrane independent of ligand-dependent engagement of FcgammaRII. We will review these data and present recent data which suggest that the role of FcgammaRIII extends beyond direct initiation of functions to a more complex role of synergistic receptor interactions. These findings will be reviewed in the context of the experimental approaches that thave been used to examine the roles of FcgammaRII and FcgammaRIII on PMN function.