Human high-affinity Fc IgG receptor (Fc gamma RI)-mediated phagocytosis and pinocytosis in COS cells.
The high-affinity receptor (Fc gamma RI) for the constant (Fc) portion of immunoglobulin G (IgG) is one of three Fc IgG receptor classes (Fc gamma Rs) found on mononuclear phagocytes. The functional specialization of each of the Fc gamma R classes is not well understood. Previous studies utilizing anti-Fc gamma R monoclonal antibodies (mAbs) as opsonins suggest that Fc gamma RI, like the other Fc gamma Rs expressed by macrophages, is able to mediate phagocytosis. The ability of Fc gamma RI to mediate pinocytosis, however, had not been certain, since it binds, but does not mediate, internalization of monomeric IgG in the monocytoid U937 cells. We studied Fc gamma RI-mediated internalization by introducing it into the Fc gamma R-negative fibroblastic COS cells. We found, using electron microscopy and fluorescence microscopy, that COS cells expressing Fc gamma RI are able to phagocytose IgG-coated zymosan particles and sheep red blood cells (SRBC), as well as pinocytose cross-linked IgG. There was no intracellular accumulation of monomeric IgG. Chimeric receptors which retain the extracellular domains of Fc gamma RI but lack the entire wild-type transmembrane and intracellular regions of the receptor mediated both phagocytosis and pinocytosis with equal or increased efficiency when compared to the wild-type receptor. Control COS cells transfected with CD2 rosetted, but did not phagocytose, SRBC. Attachment of phagocytic targets to COS cells is therefore not sufficient for phagocytosis. Taken together, this suggests that the extracellular domain of Fc gamma RI is sufficient for it to mediate phagocytosis and pinocytosis in this system.
Socolovsky
M
M
Physiological Laboratory, University of Cambridge, United Kingdom.
Hockaday
A R
AR
Allen
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D005347:Fibroblasts / Q000502:physiology*; D007127:Immunoglobulin Constant Regions / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism*; D008969:Molecular Sequence Data; D010587:Phagocytosis; D010873:Pinocytosis; D017452:Receptors, IgG / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012397:Rosette Formation; D012756:Sheep; D015054:Zymosan / Q000276:immunology
D007127:Immunoglobulin Constant Regions; D007074:Immunoglobulin G; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D015054:Zymosan