Effect of IgG for intravenous use on Fc receptor-mediated phagocytosis by human monocytes.
Polyspecific IgG given intravenously at high doses (IVIG) is used for immunomodulatory therapy in autoimmune diseases such as idiopathic thrombocytopenic purpura and myasthenia gravis. It is assumed that the clinical effect is brought about in part by a modulation of mononuclear phagocyte function, in particular by an inhibition of Fc receptor (FcR) mediated phagocytosis. In the present study, the effect of IVIG on FcR-mediated phagocytosis by monocytes was analysed in vitro. Since monocytes exposed to minute amounts of surface-bound IgG displayed impaired phagocytosis of IgG-coated erythrocytes (EA), the effect of IVIG was studied with mononuclear cells suspended in teflon bags in medium containing 10% autologous serum and IVIG (2-10 mg/ml). Monocytes pre-exposed to IVIG and then washed, displayed impaired ingestion of EA when compared with control cells cultured in 10% autologous serum only. The decrease in phagocytosis was observed with sheep erythrocytes treated with either rabbit IgG or bovine IgG1 and with anti-D-treated human erythrocytes. This suggests that phagocytosis via both FcR type I (FcRI) and type II (FcRII) was decreased. The impairment of phagocytosis was dependent on the presence of intact IgG and was mediated by IVIG from nulliparous donors and from multigravidae to the same extent, suggesting that alloantibodies contained in IVIG have a minor role in modulating FcR-mediated phagocytosis by monocytes. A flow cytometric analysis using anti-FcRI, FcRII and FcRII monoclonal antibodies showed that IVIG treatment upregulated FcRI expression but did not significantly alter the expression of FcRII and FcRIII.
Jungi
T W
TW
Institute of Veterinary Virology, University of Berne, Switzerland.
Brcic
M
M
Kuhnert
P
P
Spycher
M O
MO
Li
F
F
Nydegger
U E
UE
D000818:Animals; D000911:Antibodies, Monoclonal; D002478:Cells, Cultured; D004731:Endotoxins / Q000032:analysis; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects* / Q000276:immunology; D011961:Receptors, Fc / Q000096:biosynthesis / Q000187:drug effects* / Q000276:immunology; D012756:Sheep
D000911:Antibodies, Monoclonal; D004731:Endotoxins; D007074:Immunoglobulin G; D011961:Receptors, Fc