Fc receptors for IgG on cultured human microglia mediate cytotoxicity and phagocytosis of antibody-coated targets.
We have utilized surgically resected human central nervous system (CNS) tissue to determine the expression and functions of Fc receptors (Fc gamma R) on individual cell types found within the CNS. We observed all three classes of Fc gamma R on microglial cells in situ and in vitro, but not on astrocytes or oligodendrocytes. Incubation of cultured microglia with immune complexes (antibody-coated red blood cells) induced phagocytosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and oxidative bursts. We also found that microglia have the capability to produce T cell stimulatory soluble mediators after Fc gamma R crosslinking. These functional responses were enhanced by pretreatment of the microglia with interferon-gamma (IFN-gamma). Our results implicate microglial effector responses triggered by interaction of Fc gamma R with opsonized antigens as potential mediators of tissue injury within the CNS. Such injury may be particularly applicable to multiple sclerosis, an inflammatory demyelinating disease characterized by intrathecal production of immunoglobulins and cytokines.
Ulvestad
E
E
Department of Microbiology and Immunology, Gade Institute, University of Bergen, Norway.
Williams
K
K
Matre
R
R
Nyland
H
H
Olivier
A
A
Antel
J
J
D000328:Adult; D000920:Antibody-Dependent Cell Cytotoxicity; D015703:Antigens, CD / Q000032:analysis; D001921:Brain / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000032:analysis; D002478:Cells, Cultured; D004827:Epilepsy / Q000601:surgery; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D017628:Microglia / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D010587:Phagocytosis; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases; D011961:Receptors, Fc / Q000096:biosynthesis / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D007074:Immunoglobulin G; D011961:Receptors, Fc; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; D010727:Phosphoric Diester Hydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase