Disease relevance of Fcgr1

• FcgammaRI(-/-) mice showed impaired hypersensitivity responses, strongly reduced cartilage destruction in an arthritis model, and impaired protection from a bacterial infection [1].
• FcgammaRI (CD64) contributes substantially to severity of arthritis, hypersensitivity responses, and protection from bacterial infection [1].
• A codominant role of Fc gamma RI/III and C5aR in the reverse Arthus reaction [2].
• HER-2/neu is overexpressed in malignant tissue of approximately 30% of patients with breast cancer, and FcgammaRI is expressed on human monocytes, macrophages, and IFN-gamma activated granulocytes [3].
• The high-affinity IgG receptor, FcgammaRI, plays a central role in antibody therapy of experimental melanoma [4].

Psychiatry related information on Fcgr1

• These results demonstrate that CD64-recruited cytotoxic effectors operate in vivo but that the (huCD64 x Id) conferred an additional anti-tumor function essential for long-term protection [5].
• We found Fc gamma RI, II and III immunoreactivity in senile plaques and on ramified microglia throughout the cortex and white matter of normal and Alzheimer's disease brains [6].

High impact information on Fcgr1

• The gamma subunit of immunoglobulin Fc receptors is an essential component of the high-affinity receptor for IgG (Fc gamma RIII) and is associated with the high-affinity receptor for IgG (Fc gamma RI) and the T cell receptor-CD3 complex [7].
• A fully penetrant immunological defect also mapped to this segment, which encodes the high-affinity Fc receptor for immunoglobulin G (IgG), Fc gamma RI [8].
• Transfer of FcRI-expressing basophils into FcRI-deficient mice restored the development of the delayed-onset allergic inflammation [9].
• By using a variety of FcgammaR(-/-) mice, we demonstrate that in the absence of FcgammaRI, the IgG2a-IC-induced cellular processes of phagocytosis, cytokine release, cellular cytotoxicity, and antigen presentation are impaired [1].
• In addition, FcR-gamma chain-deficient mice were found to express partially functional FcgammaRI [10].

Biological context of Fcgr1

• Among seven NOD-related strains studied, the IIS mouse was found to possess a recombinant Idd10 interval with the same sequence at Fcgr1 as the NOD mouse, but a different sequence at Cd101 from that in the NOD mouse with 10 amino acid substitutions [11].
• Antigen presentation by human monocytes was recently found to be enhanced in vitro through the high-affinity Fc receptor for IgG (Fc gamma RI; CD64), which is exclusively present on myeloid cells [12].
• To evaluate whether specific targeting of antigens to Fc gamma RI can induce enhanced antibody responses, mice were immunized with an anti-human Fc gamma RI antibody containing antigenic determinants [12].
• To study whether this up-regulation of FcgammaRI mediates aggravation of cartilage destruction, ICA was raised in FcgammaRI(-/-) and their wild-type controls [13].
• Sequence analysis of the gene showed that six exons account for the entire Fc gamma RI cDNA sequences including the 5'- and 3'-untranslated sequences [14].

Anatomical context of Fcgr1

• Using various FcgammaR-deficient mice, we have obtained suggestive evidence that FcgammaRI on macrophages is responsible for severe cartilage destruction during arthritis mediated by immune complexes (ICs) [13].
• The human (h)IgG1, hIgG3, and hIgG4, as well as mouse (m)IgG2a and mIgG3 anti-CD3 mAb induced an Fc gamma RI (CD64)-dependent T cell proliferation in all donors [15].
• Since Fc gamma RI is not detectable on untreated neutrophils and is induced by IFN-gamma on these cells, lysis of HC 32.2A by IFN-gamma-activated neutrophils correlated with receptor induction [16].
• Fc gamma RI and Fc gamma RII on monocytes and granulocytes are cytotoxic trigger molecules for tumor cells [16].
• Of great interest, chondrocyte death remained low in FcgammaRI(-/-) [13].

Associations of Fcgr1 with chemical compounds

• DEX did not modulate the rate of decay of the Fc gamma RI mRNA, suggesting that the up-regulatory effect of DEX may occur, in part, at the level of transcription [17].
• Endocytosis of heat-aggregated IgG (HA-IgG) by COS-1 cells stably transfected with FcgammaRIIA or chimeric FcgammaRI-gamma-gamma (EC-TM-CYT) was not significantly altered by PP2, piceatannol, or wortmannin [18].
• This study shows that aggregation of U937 cell high affinity IgG Fc receptor (Fc gamma RI) results in the transient tyrosine phosphorylation of Fc gamma RI gamma-chain but not the phosphorylation of gamma-chains associated with nonaggregated IgA Fc receptors (Fc alpha R) on the same cells [19].
• Sequence analysis of cDNA clones indicates that mouse Fc gamma RI is a transmembrane glycoprotein that is composed of three disulfide bonded extracellular Ig binding domains unlike Fc gamma RII of man and mouse [20].
• In contrast, aggregation of Fc gamma RI in the presence of vanadate induced the sustained tyrosine phosphorylation of Fc gamma RI gamma-chains and the rapid and extensive phosphorylation of nonaggregated Fc alpha R gamma-chains and low affinity IgG Fc receptors (Fc gamma RII) [19].

Physical interactions of Fcgr1

• Furthermore, HCC49x H22 was shown to simultaneously bind to KLEB cells and a soluble FcgammaRI fusion protein, demonstrating the bifunctional nature of the molecule [21].
• Because of mutations in the Fc gamma RI and C'1q binding sites of the Fc portion of the murine CTLA4/Fc fusion protein, the molecule binds to, but does not target, cells for Ab-dependent cellular cytotoxicity or complement-directed cytolysis [22].

Regulatory relationships of Fcgr1

• We, therefore, propose that FcgammaRIIb serves to inhibit FcgammaRI/IIa-mediated macrophage activation using SHIP as its effector [23].
• Local overexpression of IFN-gamma induced increased FcgammaRI mRNA levels in synovium [13].
• ApoE(-/-) mice have higher levels of activating FcgammaRI and FcgammaRIIIA, and inhibitory FcgammaRIIB, compared with wild-type mice [24].
• Thus, binding to the tumor target via this Fc receptor does not lead to lysis and may initiate signals distinct from those triggered through Fc gamma RI or Fc gamma RII [16].
• Blocking studies indicated that the residual anemic phenotype induced by 34-3C in the absence of FcgammaRIII reflects an activation of FcgammaRI that is normally coexpressed with FcgammaRIII on macrophages [25].

Other interactions of Fcgr1

• The high-affinity receptor for IgG, FcgammaRI, shares its capacity to bind IgG2a immune complexes (IgG2a-IC) with the low-affinity receptor FcgammaRIII and complement factors, hampering the definition of its biological role [1].
• Induction of intracellular Ca2+ mobilization and cytotoxicity by hybrid mouse monoclonal antibodies. Fc gamma RII regulation of Fc gamma RI-triggered functions or signaling [26]?
• FcgammaRI up-regulation induced by local adenoviral-mediated interferon-gamma production aggravates chondrocyte death during immune complex-mediated arthritis [13].
• In a previous study we found that if a chronic T-cell-mediated antigen-induced arthritis (AIA) was elicited in knee joints of FcR gamma-chain-deficient mice that lack functional Fc gamma RI and Fc gamma RIII, joint inflammation was comparable but severe cartilage destruction was absent [27].
• In this paper, we demonstrate that, in response to IgG immune complex formation, FcgammaRI/III- and C5aR-mediated pathways are both necessary and only together are they sufficient to trigger the full expression of inflammation in skin and lung [2].

Analytical, diagnostic and therapeutic context of Fcgr1

• FcgammaRI- and III-deficient mice, as well as the combined FcgammaRI, II, and III knockout mice, were protected by passive immunization, indicating FcR not to be essential for protection [28].
• Southern blot analysis had shown that the mouse Fc gamma RI gene is a single copy gene with no RFLP in inbred strains of mice, but analysis of an intersubspecies backcross of mice showed that unlike other mouse FcR genes which are on mouse chromosome 1 the locus encoding Fc gamma RI, termed Fcg1, is located on chromosome 3 [14].
• Additionally, these data demonstrate the potential utility of ADCC as a viable approach for targeting vaccination strategies that promote FcgammaRI/III scavenging pathways against cancer [29].
• Flow cytometry shows that IFN-gamma downregulates the IL-6-induced expression of IL-4R whereas it has no such effect on the high-affinity receptors for monomeric IgG2a (Fc gamma RI) [30].
• The biological consequences of FcgammaRI ligation were determined in both in vitro and in vivo models of inflammation and sepsis [31].

References