Fc gamma receptors (FcγRs) are critical effector receptors for immunoglobulin G (IgG) antibodies. On macrophages, FcγRs mediate multiple effector functions, including phagocytosis, but the individual contribution of specific FcγRs to phagocytosis has not been fully characterized. Primary human macrophage populations, such as splenic macrophages, can express FcγRI, FcγRIIA, and FcγRIIIA. However, there is currently no widely available monocyte or macrophage cell line expressing all these receptors. Common sources of monocytes for differentiation into macrophages, such as human peripheral blood monocytes and the monocytic leukemia cell line THP-1, generally lack the expression of FcγRIIIA (CD16A). Here, we utilized a lentiviral system to generate THP-1 cells stably expressing human FcγRIIIA (CD16F158). THP-1-CD16A cells treated with phorbol 12-myristate 13-acetate for 24 hours phagocytosed anti-D-opsonized human red blood cells primarily utilizing FcγRI with a lesser but significant contribution of IIIA while phagocytosis of antibody-opsonized human platelets equally utilized FcγRI and Fcγ IIIA. Despite the well-known ability of FcγRIIA to bind IgG in cell free systems, this receptor did not appear to be involved in either RBC or platelet phagocytosis. These transgenic cells may constitute a valuable tool for studying macrophage FcγR utilization and function.
The accelerated clearance of platelets is a central feature of immune thrombocytopenia (ITP) pathophysiology. The Harrington-Hollingsworth experiment provided evidence that accelerated platelet clearance may be due to factors present in ITP patient circulation. Harrington et al. demonstrated that the transfusion of ITP patient blood or plasma can produce a precipitous platelet count decrease in non-ITP recipients.1 It was hypothesized that circulating "thrombocytopenic factors" were responsible for the platelet count decreases and thus also in ITP.1 Overall, the transfusion of ITP blood or its plasma equivalent produced a >50% recipient platelet count decrease in 16 of 26 (61.5%) of such instances.2 Subsequent work by Shulman et al. provided more direct evidence that anti-platelet immunoglobulin G (IgG) autoantibodies are a thrombocytopenic factor in ITP.3 Anti-platelet autoantibodies are thought to opsonize platelets and trigger clearance by macrophage phagocytosis,4,5 particularly in the spleen which is the dominant site of platelet clearance in ITP.6 It is now appreciated that IgG autoantibodies in ITP target multiple platelet antigens including glycoprotein (GP)IIb/IIIa, GPIb/IX, GPV, and GPIa/IIa.7-10 More recently, it has been demonstrated that C-reactive protein can enhance the phagocytosis of blood cells such as erythrocytes11 and platelets,12 and may potentially be a thrombocytopenic factor in ITP.
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