Article

Fc receptors and their interactions with immunoglobulins.

Division of Biology, Howard Hughes Medical Institute, California Institute of Technology, Pasadena 91125, USA.
Annual Review of Cell and Developmental Biology (Impact Factor: 20.24). 02/1996; 12:181-220. DOI: 10.1146/annurev.cellbio.12.1.181
Source: PubMed

ABSTRACT Receptors for the Fc domain of immunoglobulins play an important role in immune defense. There are two well-defined functional classes of mammalian receptors. One class of receptors transports immunoglobulins across epithelial tissues to their main sites of action. This class includes the neonatal Fc receptor (FcRn), which transports immunoglobulin G (IgG), and the polymeric immunoglobulin receptor (pIgR), which transports immunoglobulin A (IgA) and immunoglobulin M (IgM). Another class of receptors present on the surfaces of effector cells triggers various biological responses upon binding antibody-antigen complexes. Of these, the IgG receptors (Fc gamma R) and immunoglobulin E (IgE) receptors (Fc epsilon R) are the best characterized. The biological responses elicited include antibody-dependent, cell-mediated cytotoxicity, phagocytosis, release of inflammatory mediators, and regulation of lymphocyte proliferation and differentiation. We summarize the current knowledge of the structures and functions of FcRn, pIgR, and the Fc gamma R and Fc epsilon RI proteins, concentrating on the interactions of the extracellular portions of these receptors with immunoglobulins.

1 Follower
 · 
105 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background The various cell types and their relative numbers in multicellular organisms are controlled by growth factors and related extracellular molecules which affect genetic expression pathways. However, these substances may have both/either inhibitory and/or stimulatory effects on cell division and cell differentiation depending on the cellular environment. It is not known how cells respond to these substances in such an ambiguous way. Many cellular effects have been investigated and reported using cell culture from cancer cell lines in an effort to define normal cellular behaviour using these abnormal cells. A model is offered to explain the harmony of cellular life in multicellular organisms involving interacting extracellular substances. Methods A basic model was proposed based on asymmetric cell division and evidence to support the hypothetical model was accumulated from the literature. In particular, relevant evidence was selected for the Insulin-Like Growth Factor system from the published data, especially from certain cell lines, to support the model. The evidence has been selective in an attempt to provide a picture of normal cellular responses, derived from the cell lines. Results The formation of a pair of coupled cells by asymmetric cell division is an integral part of the model as is the interaction of couplet molecules derived from these cells. Each couplet cell will have a receptor to measure the amount of the couplet molecule produced by the other cell; each cell will be receptor-positive or receptor-negative for the respective receptors. The couplet molecules will form a binary complex whose level is also measured by the cell. The hypothesis is heavily supported by selective collection of circumstantial evidence and by some direct evidence. The basic model can be expanded to other cellular interactions. Conclusions These couplet cells and interacting couplet molecules can be viewed as a mechanism that provides a controlled and balanced division-of-labour between the two progeny cells, and, in turn, their progeny. The presence or absence of a particular receptor for a couplet molecule will define a cell type and the presence or absence of many such receptors will define the cell types of the progeny within cell lineages.
    Theoretical Biology and Medical Modelling 09/2014; 11:40-40. DOI:10.1186/1742-4682-11-40 · 1.27 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Trastuzumab has been used for the treatment of HER2-overexpressing breast cancer for more than a decade, but the mechanisms of action for the therapy are still being actively investigated. Ab-dependent cell-mediated cytotoxicity mediated by NK cells is well recognized as one of the key mechanisms of action for trastuzumab, but trastuzumab-mediated Ab-dependent cellular phagocytosis (ADCP) has not been established. In this study, we demonstrate that macrophages, by way of phagocytic engulfment, can mediate ADCP and cancer cell killing in the presence of trastuzumab. Increased infiltration of macrophages in the tumor tissue was associated with enhanced efficacy of trastuzumab whereas depletion of macrophages resulted in reduced antitumor efficacy in mouse xenograft tumor models. Among the four mouse FcγRs, FcγRIV exhibits the strongest binding affinity to trastuzumab. Knockdown of FcγRIV in mouse macrophages reduced cancer cell killing and ADCP activity triggered by trastuzumab. Consistently, an upregulation of FcγRIV expression by IFN-γ triggered an increased ADCP activity by trastuzumab. In an analogous fashion, IFN-γ priming of human macrophages increased the expression of FcγRIII, the ortholog of murine FcγRIV, and increased trastuzumab-mediated cancer cell killing. Thus, in two independent systems, the results indicated that activation of macrophages in combination with trastuzumab can serve as a therapeutic strategy for treating high HER2 breast cancer by boosting ADCP killing of cancer cells.
    The Journal of Immunology 01/2015; 194:4379-4386. · 5.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Since anti-tumor necrosis factor (TNF) antibodies were introduced to treat patients with inflammatory bowel diseases, short- and long-term clinical and endoscopic endpoints can be achieved that were unreachable with conventional anti-inflammatory agents. Although a large proportion of patients (70-90%) initially respond to the treatment, remission rates after induction are still low (20-50%) and patients are at risk to lose response to the drug over time. This inter-individual variability in response is likely to be influenced by the observed inter-individual variability in pharmacokinetics. By extensively reviewing the literature, we evaluated the potential role of therapeutic drug monitoring to optimize dosing of anti-TNF drugs. Thereby we emphasize some of the pharmacokinetic cornerstones that can help to understand the observed concentration-effect relationship. After discussing some of the most commonly used assays to measure anti-TNF drug and anti-drug antibody concentrations, we reviewed the application of those tests and their potential clinical value in retrospective and prospective studies. © 2015, The American College of Clinical Pharmacology.
    The Journal of Clinical Pharmacology 03/2015; 55 Suppl 3(S3):S39-50. DOI:10.1002/jcph.374 · 2.47 Impact Factor

Preview

Download
2 Downloads
Available from