The primate erythrocyte complement receptor (CR1) as a privileged site: binding of immunoglobulin G to erythrocyte CR1 does not target erythrocytes for phagocytosis.
The primate erythrocyte (E) complement receptor, CR1, is a transmembrane glycoprotein located in clusters on the surface of E. In vivo studies have demonstrated that during processing and clearance of complement-opsonized immune complexes, large amounts of immunoglobulin G (IgG) can be bound to primate E via CR1 with no E loss or lysis. However, when comparable amounts of IgG are bound to other sites on E, in many cases the E are cleared from the circulation by the mononuclear phagocytic system. Therefore, due to its role in immune complex processing, CR1 may represent a privileged site on the primate E. To delineate further this property of E CR1, we performed in vitro phagocytosis assays in the absence of complement and examined the ingestion of E, opsonized at various sites with IgG, by peripheral blood monocytes. When either human or rhesus monkey E were opsonized at sites other than CR1, with between 1,000 and 15,000 IgG per E, substantial phagocytosis of E was evident. However, when comparable amounts of IgG were bound exclusively via CR1, little, if any, phagocytosis was observed. The key to the low phagocytic level of E opsonized via CR1 may be related to the requirements of a "zipper mechanism" for phagocytosis first annunciated by Griffin et al. Based on their findings, we suggest that due to the presence of preexisting clusters of CR1 on the E membrane, large amounts of IgG can be bound to E under conditions that preclude circumferential engagement (and phagocytosis) of the entire E by Fc receptors on the monocyte.
Reinagel
M L
ML
Department of Biochemistry, University of Virginia School of Medicine, Charlottesville 22908, USA.
Gezen
M
M
Ferguson
P J
PJ
Kuhn
S
S
Martin
E N
EN
Taylor
R P
RP
D000818:Animals; D001665:Binding Sites / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D011817:Rabbits; D017463:Receptors, Complement 3b / Q000097:blood* / Q000276:immunology; D012756:Sheep; D013045:Species Specificity
D007074:Immunoglobulin G; D017463:Receptors, Complement 3b