Disease relevance of Fcr

• The classical model for this immunopathological cascade, the Arthus reaction, was reinvestigated with a murine strain deficient in Fc receptor expression [1].
• However, the disruption of a single gene, which encodes the gamma chain of the Fc receptor, was found to achieve this uncoupling in a spontaneous model of lupus nephritis, the New Zealand Black/New Zealand White (NZB/NZW) mouse [2].
• Linkage on chromosome 3 of autoimmune diabetes and defective Fc receptor for IgG in NOD mice [3].
• These data suggest that Fc receptors play an integral role in the pathogenesis of type II hypersensitivity and suggest potential therapeutic benefits of Fc receptor blockade [4].
• Hypopigmentation occurred in mice deficient in activating FcR containing the common gamma subunit (Fc gamma R gamma(-/-)) and in mice deficient in the C3 complement component [5].

High impact information on Fcr

• This restoration of activity does not depend on the tyrosine residues in the beta cytoplasmic tail, implying that antigen receptor-mediated presentation can occur by a pathway distinct from that used by the Fc receptor Fc gamma RIII [6].
• Mouse macrophages and lymphocytes express two distinct isoforms of a single class of Fc receptor for IgG [7].
• Prolongation of graft survival is dependent on both complement- and Fc receptor-mediated mechanisms in a major histocompatibility complex (MHC)-mismatched skin transplant model [8].
• Primary macrophages isolated from mer(kd) mice showed that the phagocytic deficiency was restricted to apoptotic cells and was independent of Fc receptor-mediated phagocytosis or ingestion of other particles [9].
• These results demonstrate that Fc-receptor-dependent mechanisms contribute substantially to the action of cytotoxic antibodies against tumors and indicate that an optimal antibody against tumors would bind preferentially to activation Fc receptors and minimally to the inhibitory partner FcgammaRIIB [10].

Chemical compound and disease context of Fcr

• This study documents an important role for the beta(2) integrin Mac-1 (CD11b/CD18) in FcR-mediated protection against melanoma [11].
• Mapping regions of herpes simplex virus type 1 glycoprotein I required for formation of the viral Fc receptor for monomeric IgG [12].
• Cyclic AMP modulation of Fc receptor expression on a pre-B cell lymphoma [13].
• Inhibition of the Fc receptor-mediated oxidative burst in macrophages by the Yersinia pseudotuberculosis tyrosine phosphatase [14].
• However, despite this loss, the residual Fc receptor-positive cells present following hemorrhage were capable of releasing enhanced levels of PGE2 [15].

Biological context of Fcr

• CH3 domain of IgG as binding site to Fc receptor on mouse lymphocytes [16].
• It has been suggested that the macrophage Fc receptor (FcR) provides an efficient route of entry of virus through the attachment of non-neutralized virus-antibody complexes and that for those viruses that escape destruction by the phagocyte, antibody results in a paradoxical increase in virus replication [17].
• However, using cloned human NK cells, we determined here that Fc receptor stimulation triggers granule release and ADCC through a PKC-independent pathway [18].
• Tyrosine phosphorylation is required for Fc receptor-mediated phagocytosis in mouse macrophages [19].
• Activation mediated by RP105 but not CD40 makes normal B cells susceptible to anti-IgM-induced apoptosis: a role for Fc receptor coligation [20].

Anatomical context of Fcr

• Polymorphism of Fc receptor on murine B cells is Igh-linked [21].
• Fc receptor-mediated antibody regulation of T cell immunity against intracellular pathogens [22].
• These results suggest that the polymorphism in the mitogenic effect of these IgG1 antibodies is caused by polymorphism in monocyte function, possibly at the level of the Fc receptor that reacts with mouse IgG1 [23].
• The NK cell isoform was not expressed on the surface of COS cells unless cotransfected with a subunit that was expressed in NK cells and that was identical to the gamma subunit of the high affinity IgE Fc receptor (Fc epsilon RI) [24].
• We found here that the inhibitory Fc receptor FcgammaRIIb was expressed on plasma cells and controlled their persistence in the bone marrow [25].

Associations of Fcr with chemical compounds

• In vitro, IAP-/- PMNs were deficient in beta3 integrin-dependent ligand binding, activation of an oxidative burst, and Fc receptor-mediated phagocytosis [26].
• We assessed the effects of exposure to immune complexes in vivo on macrophages' Fc receptor function and C3 receptor function [27].
• J774 FcR was judged to be a glycoprotein based on the sensitivity of its isoelectric point to neuraminidase digestion, its labeling with galactose oxidase/NaB[3H4], and its binding to concanavalin A-Sepharose [28].
• Such characteristic cytotoxic spectra, as well as serological phenotypes (Thy-1+, Lyt-1-2-, asialo GM1-positive, T200+, TdT-, Fc receptor-positive) indicated that these LGL clones exactly represent endogenous NK cells, rather than a variety of anomalous killer cells generated in various culture conditions [29].
• Although the Src homology 2 domain-containing 5' inositol phosphatase (SHIP) is a well-known mediator of inhibitory signals after B cell antigen receptor (BCR) coaggregation with the low affinity Fc receptor, it is not known whether SHIP functions to inhibit signals after stimulation through the BCR alone [30].

Physical interactions of Fcr

• Results demonstrate the SHIP is the predominant intracellular ligand for the phosphorylated Fc gamma RIIB1 ITIM, although the SHP-2 decoy exhibits some ability to bind Fc gamma RIIB1 and block Fc receptor function [31].
• Furthermore, suppression was not limited to Fc receptor-mediated phagocytosis because binding and uptake of C3bi-opsonized SRBCs to CR3 receptors was also decreased following LPS treatment [32].
• A major histocompatibility complex class I-like Fc receptor cloned from human placenta: possible role in transfer of immunoglobulin G from mother to fetus [33].
• These data indicate that Fc receptor binding of IgG2b results from the concerted action of membrane lipid and protein [34].

Regulatory relationships of Fcr

• Aggregation of the high-affinity Fc receptor (FcepsilonRI) for immunoglobulin E (IgE) in MC/9 mouse mast cells stimulates the synthesis and secretion of tumor necrosis factor alpha (TNF-alpha) [35].
• We investigated the cytolytic mechanism by CD4+ T cells in anti-CD3 mAb-induced redirected cytotoxicity against a murine Fc receptor-bearing mastocytoma (P815) transfected with either CD80 or CD137 ligand (CD137L) [36].
• The B cell inhibitory Fc receptor triggers apoptosis by a novel c-Abl family kinase-dependent pathway [37].
• Opposing effects of glucocorticoids on interferon-gamma-induced murine macrophage Fc receptor and Ia antigen expression [38].
• Mouse anti-human CD3 (T3) antibodies can induce T cell proliferation in the presence of Fc receptor (FcR)-bearing accessory cells [39].

Other interactions of Fcr

• Thus, separate receptors mediate these stimulations, and Fc receptor cross-linkage is required for IL-4 production [40].
• The synthesis and release of CSF-1 and MCP-1 by mesangial cells as a consequence of Fc receptor occupancy may be responsible for macrophage recruitment and activation at sites of immune-complex deposition [41].
• The increase of mRNA for CSF-1 and MCP-1 was not reduced by either cytochalasin B or D, indicating that Fc receptor occupancy is sufficient for signaling and that phagocytosis is not required to elicit this response [41].
• Nevertheless, cells derived from PAM cultures in media containing IL-3 displayed a high degree of heterogeneity in terms of their Fc receptor-mediated phagocytic activity [42].
• Finally, we evaluated the relative importance of the Fc receptor versus the complement pathway in disposing antibody-opsonized DAF/Crry-deficient erythrocytes [43].

Analytical, diagnostic and therapeutic context of Fcr

• The innate mononuclear phagocyte network depletes B lymphocytes through Fc receptor-dependent mechanisms during anti-CD20 antibody immunotherapy [44].
• Here we show that tyrosine phosphorylation is an early event after Fc receptor ligation in mouse inflammatory macrophages, and that the formation of tyrosine phosphoproteins coincides temporally with the appearance of F-actin beneath phagocytic cups [19].
• The role of nonclassical Fc receptor-associated, Ag-B antigens (Ia) in rat allograft enhancement [45].
• The IgG Fc receptor II on human monocytes is polymorphic in its ability to bind mIgG1, and its isoelectric focusing pattern [46].
• Effector cells capable of mediating cytotoxicity in each assay were defined by testing the cytotoxic function of lymphocyte subpopulations isolated from two representative patients with each disease using techniques of immunoabsorbent affinity chromatography and Fc receptor binding to antigen-antibody complexes [47].

References