THE HIGH-AFFINITY FC-GAMMA RECEPTOR (CD64) INDUCES PHAGOCYTOSIS IN THE ABSENCE OF ITS CYTOPLASMIC DOMAIN - THE GAMMA-SUBUNIT OF FC-GAMMA-RIIIA IMPARTS PHAGOCYTIC FUNCTION TO FC-GAMMA-RI

The high affinity Fc gamma receptor, Fc gamma RI, is unique among the three classes of macrophage Fc gamma receptors not only in its affinit y for IgG, but also in the structure of its cytoplasmic domain. Fc gam ma RIIA and the gamma subunit of Fc gamma RIIIA have tyrosine-containi ng motifs within their cytoplasmic domains that are phosphorylated whe n crosslinked and that are required for phagocytosis by COS-1 cell tra nsfectants. In contrast to these other Fc gamma receptors, Fc gamma RI does not contain cytoplasmic tyrosines and does not induce phagocytos is in COS-1 transfectants. We transfected wild-type (WT) and mutant (M T) Fc gamma RI lacking the cytoplasmic domain into COS-1 cells and mur ine macrophages and assessed phagocytosis using IgG-coated red blood t ells (RBCs) and RBCs conjugated with Fab anti-human Fc gamma RI monocl onal antibody (mAb). Fc gamma RI, in contrast to Fc gamma RIIA, did no t induce phagocytosis in COS cells. However, both WT and MT Fc gamma R I induced phagocytosis in murine macrophages, and phagocytosis was inh ibited by the tyrosine kinase inhibitor tyrphostin 23. Human monocytes also phagocytosed Fc gamma RI-targeted RBCs, and activation of Fc gam ma RI on monocytes with Fab anti-Fc gamma RI induced phosphorylation o f Fc gamma RII on tyrosine residues. However, Fc gamma RI activation o f Fc gamma RI-Fc gamma RIIA COS-1 cotransfectants did not induce tyros ine phosphorylation of Fc gamma RIIA, and coexpression of Fc gamma RI and Fc gamma RIIA in COS cells did not confer Fc gamma RI phagocytic c apability. In contrast, coexpression in COS-1 cells of Fc gamma RI wit h the gamma subunit of Fc gamma RIIIA conferred phagocytic function to both Fc gamma RI and the MT Fc gamma RI lacking the cytoplasmic domai n. Thus, Fc gamma RI does not require its cytoplasmic domain to mediat e a phagocytic signal and interacts with the gamma subunit of Fc gamma RIIIA to induce phagocytosis.