THE PRIMATE ERYTHROCYTE COMPLEMENT RECEPTOR (CR-1) AS A PRIVILEGED SITE - BINDING OF IMMUNOGLOBULIN-G TO ERYTHROCYTE CR-1 DOES NOT TARGET ERYTHROCYTES FOR PHAGOCYTOSIS

The primate erythrocyte (E) complement receptor, CR1, is a transmembra ne glycoprotein located in clusters on the surface of E. In vivo studi es have demonstrated that during processing and clearance of complemen t-opsonized immune complexes, large amounts of immunoglobulin G (IgG) can be bound to primate E via CR1 with no E loss or lysis. However, wh en comparable amounts of IgG are bound to other sites on E. in many ca ses the E are cleared from the circulation by the mononuclear phagocyt ic system. Therefore, due to its role in immune complex processing, CR 1 may represent a privileged she an the primate E. To delineate furthe r 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 exclusivel y via CR1, little, if any, phagocytosis was observed. The key to the l ow phagocytic level of E opsonized via CR1 may he related to the requi rements of a ''zipper mechanism'' for phagocytosis first annunciated b y Griffin et al. Based on their findings, we suggest that due to the p resence of preexisting clusters of CR1 on the E membrane, large amount s of IgG can be bound to E under conditions that preclude circumferent ial engagement (and phagocytosis) of the entire E by Fc receptors on t he monocyte. (C) 1997 by The American Society of Hematology.