Monoclonal antibodies identify three IgG Fc receptors in normal human central nervous system.

Functional Fc receptors have been described in the central nervous system (CNS) in the subependymal periventricular regions, leptomeninges, including brain perivascular tissues, and choroid plexus. The distribution of this receptor activity suggests a role in protection of adjacent nervous tissue from IgG-opsonized antigens, including microorganisms. In this report, we have utilized monoclonal antibodies to human Fc gamma RI, II, and III; 32, IV.3, and 3G8, respectively, to immunohistochemically examine the distribution of these receptors in the CNS. Fc gamma RI was only occasionally present in the CNS where it was identified most often in the choroid plexus. Fc gamma RII was the predominant receptor in brain. It as consistently present in leptomeninges, including brain perivascular regions, arachnoid granulations, and choroid plexus stroma. Some samples of subependymal periventricular tissue also displayed Fc gamma RII. Fc gamma RIII was only identified in subependymal periventricular tissue but not in choroid plexus and arachnoid. These results demonstrate that regions of normal adult brain which produce cerebral spinal fluid (CSF) and border on CSF and vascular compartments display Fc gamma R heterogeneity consistent with that of blood monocytes and systemic macrophages.

Fc receptor-mediated binding and ingestion of immunoglobulin G-coated erythrocytes by the epithelium of the posterior ciliary processes: an in-vitro study.

In the present in vitro study of intact ciliary processes, we observed, under differential interference microscopy, IgG inhibitable selective epithelial adherence and internalization of IgG-coated erythrocytes (E-IgG). Unequivocal evidence of ligand ingestion was obtained with a fluorescence technique which employed glutaraldehyde-fixed opsonized erythrocytes. Neither adherence nor internalization were seen when uncoated erythrocytes, IgM, or F (ab')2-coated erythrocytes were substituted for E-IgG in the incubation media. These in-vitro studies demonstrated that the cell membranes of this epithelium exhibit a specific receptor for IgG which may clear the aqueous of IgG aggregates and be associated with the exocytosis of soluble mediators of inflammation.

Characterization of immunoglobulin G-Fc receptor activity in the outflow system of the cerebrospinal fluid.

We have examined IgG Fc receptor (FcR) activity of human and rabbit arachnoid granulations and leptomeninges using antibody (IgG)-coated erythrocytes (EIgG), covalently crosslinked IgG dimers, trimers and oligomers, immune complexes, aggregated Fc fragments and a monoclonal anti-human neutrophil Fc receptor antibody, 3G8. EIgG bound specifically to cells of the leptomeninges and arachnoid granulations; uncoated erythrocytes, F(ab')2-coated, or IgM-coated erythrocytes failed to bind. The specificity of this interaction was demonstrated by inhibition studies. Monomeric IgG and Fc fragments blocked EIgG adherence, whereas bovine serum albumin (BSA), Fab fragments of IgG and the monoclonal anti-neutrophil FcR antibody failed to inhibit EIgG adherence. Monomeric IgG inhibited FcR function in a dose-dependent fashion; maximal inhibition was achieved at 1.7 X 10(-5)M IgG, indicating a relatively low avidity receptor. Oligomers of IgG inhibited EIgG adherence more effectively and inhibition was directly related to oligomer size. Additionally, these tissues were positive for specific and non-specific esterases. These studies suggest that the CSF pathway from the perivascular spaces to the arachnoid granulations plays a protective role in the clearance of IgG and IgG immune complexes in infections and immune-mediated disorders.

High avidity periventricular IgG-Fc receptor activity in human and rabbit brain.

Periventricular tissues from human and rabbit brains were examined for receptors for the Fc domain of immunoglobulin G (Fc receptors). Fc receptors were demonstrated using antibody-coated erythrocytes (EIgG) and covalently cross-linked rabbit IgG. EIgG adhered specifically to nonneuronal periventricular glial areas and was inhibited by IgG and Fc fragments, but not by Fab fragments or albumin. EIgG adherence was 50% inhibited with 6.7 X 10(-9) M IgG. This is 1/1000 the amount of IgG required to produce 50% inhibition of EIgG adherence to arachnoid FcR. Studies with covalently cross-linked IgG demonstrated a linear relationship between ligand size and inhibition of EIgG adherence. Uncoated erythrocytes, IgM-coated erythrocytes, or F(ab')2-coated erythrocytes failed to bind to periventricular tissue. Many nonspecific esterase-positive cells were found in the area of periventricular EIgG adherence; this esterase activity was sensitive to fluoride. These results provide, for the first time, evidence of inherent IgG receptor activity in the periventricular tissues, and suggest that the periventricular tissues play a protective role in the removal of IgG or IgG-antigen complexes which have entered the cerebral spinal fluid.