Normal polyclonal immunoglobulins ('IVIg') inhibit microglial phagocytosis in vitro.
Phagocytosis removes pathogens and tissue debris during inflammatory reactions, but also plays an important role in autoimmune reactions. The main phagocytes in the central nervous system (CNS) are microglial cells that are activated during CNS inflammation. In the treatment of inflammatory demyelinating diseases like multiple sclerosis (MS), administration of intravenous immunoglobulins (IVIg) has become a promising immunomodulatory therapy. Although a large number of potential mechanisms for the effects of IVIg has been suggested, the precise mode of action in CNS inflammation is unknown. We assessed the influence of IVIg on phagocytosis and endocytosis in microglia in vitro. IVIg had little effect on non-specific phagocytosis of latex particles in untreated microglia, while there was a dose-dependent inhibition in microglia activated with LPS and IFNgamma. Endocytosis of soluble myelin basic protein (MBP) was downregulated by IVIg in both untreated and activated microglia. The effect was mediated by an F(ab')(2) preparation of immunoglobulins, suggesting that Fc receptor-mediated phagocytosis is not involved. Intact IVIg, but not F(ab')(2) fragments also suppressed Fc receptor-mediated phagocytosis of opsonised erythrocytes in both untreated and activated microglia. These results show that IVIg can inhibit the phagocytic activity of microglia via different mechanisms. Such an effect could contribute to the immunomodulatory capacity of IVIg in inflammatory CNS diseases.
Stangel
M
M
E.D. Adrian Building, Robinson Way, Forvie Site, Cambridge, UK. mstangel@zedat.fu-berlin.de
Joly
E
E
Scolding
N J
NJ
Compston
D A
DA
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011961:Receptors, Fc / Q000502:physiology
D007140:Immunoglobulin Fab Fragments; D016756:Immunoglobulins, Intravenous; D008070:Lipopolysaccharides; D011961:Receptors, Fc; D007371:Interferon-gamma