Fc Receptor Phagocytosis

Worth, Randall G.; Schreiber, Alan D.

doi:10.1007/978-0-387-28669-3_3

Cited by 2 publications

(5 citation statements)

References 176 publications

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“…Fc-gamma receptors (Fc␥Rs) are essential for the recognition and elimination of immunoglobulin G (IgG)-opsonized patho-gens and immune complexes, as well as clearance of senescent erythrocytes and platelets. They are important for immune surveillance mechanisms and have been implicated in immunohematologic and autoimmune disorders [1][2][3][4][5]. Fc␥Rs bind to the constant region of IgG and mediate downstream events that are intimately linked to the size of the opsonized complex.…”

Section: Introductionmentioning

confidence: 99%

“…Members of the human Fc␥R family can be divided into four subclasses (Fc␥RI, Fc␥RII, Fc␥RIII, and Fc␥RIV) based on size, affinity for IgG, biochemical structure, reactivity with mAbs, and cellular and tissue distribution [1,2,17]. Among the activating Fc␥Rs, Fc␥RI and Fc␥RIIA illustrate different structural requirements for induction of signaling events.…”

Section: Introductionmentioning

confidence: 99%

“…Among the activating Fc␥Rs, Fc␥RI and Fc␥RIIA illustrate different structural requirements for induction of signaling events. Fc␥RI functions as a multichain heterocomplex composed of a ligand binding ␣ chain and a signal-transducing ␥ subunit [1]. Central to the initiation of ␥-chain signaling is a classic immunoreceptor tyrosine-based activation motif (ITAM) consisting of two YxxL sequences separated by seven amino acids [18].…”

Section: Introductionmentioning

confidence: 99%

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Differential kinase requirements in human and mouse Fc-gamma receptor phagocytosis and endocytosis

Huang

Barreda

Worth

et al. 2006

Journal of Leukocyte Biology

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Fc gamma receptors (FcgammaRs) contribute to the internalization of large and small immune complexes through phagocytosis and endocytosis, respectively. The molecular processes underlying these internalization mechanisms differ dramatically and have distinct outcomes in immune clearance and modulation of cell function. However, it is unclear how the same receptors (FcgammaR) binding to identical ligands (IgG) can elicit such distinct responses. We and others have shown that Syk kinase, Src-related tyrosine kinases (SRTKs) and phosphatidyl inositol 3-kinases (PI3K) play important roles in FcgammaR phagocytosis. Herein, we demonstrate that these kinases are not required for FcgammaR endocytosis. 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. In contrast, phagocytosis of large opsonized particles (IgG-sensitized sheep erythrocytes, EA) was markedly reduced by these inhibitors. These results were confirmed in primary mouse bone marrow-derived macrophages and freshly isolated human monocytes. Levels of receptor phosphorylation were similar when FcgammaRIIA was cross-linked using HA-IgG or EA. However, inhibition of FcgammaR phosphorylation prevented only FcgammaR phagocytosis. Finally, biochemical analyses of PI3K(p85)-Syk binding indicated that direct interactions between native Syk and PI3K proteins are differentially regulated during FcgammaR phagocytosis and endocytosis. Overall, our results indicate that FcgammaR endocytosis and phagocytosis differ dramatically in their requirement for Syk, SRTKs, and PI3K, pointing to striking differences in their signal transduction mechanisms. We propose a competitive inhibition-based model in which PI3K and c-Cbl play contrasting roles in the induction of phagocytosis or endocytosis signaling cascades.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Differential kinase requirements in human and mouse Fc-gamma receptor phagocytosis and endocytosis

Huang

Barreda

Worth

et al. 2006

Journal of Leukocyte Biology

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“…Both activating (FcγRI, FcγRIIA, FcγRIII) and inhibitory (FcγRIIB) FcγRs participate in phagocytosis of IgG-coated particles, allowing for strict self-regulation among the FcR classes through cytoplasmic activation and inhibition motifs [10; 11]. FcγRIIA is a 40 kDa transmembrane receptor found on neutrophils, monocytes, macrophages, dendritic cells and platelets [12]. FcγRIIA can initiate phagocytosis of large IgG-coated targets or endocytosis of small IgG containing immune complexes.…”

Section: Introductionmentioning

confidence: 99%

“…Most signaling is initiated by the immunoreceptor tyrosine based activation motif (ITAM) sequence located in the cytoplasmic domain. The ITAM of FcγRIIA is slightly different than traditional ITAM sequences due to the extra intervening residues between the dual YxxL motifs (Y-M-T-L-12aa -Y-L-T-L) and is therefore referred to as an ITAM-like region (reviewed in[12]).…”

Section: Introductionmentioning

confidence: 99%

Differential requirement of lipid rafts for FcγRIIA mediated effector activities

Vieth

Kim

Pan

et al. 2010

Cellular Immunology

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Immunoglobulin G (IgG) dependent activities are important in host defense and autoimmune diseases. Various cell types including macrophages and neutrophils contribute to pathogen destruction and tissue damage through binding of IgG to Fcγ receptors (FcγR). One member of this family, FcγRIIA, is a transmembrane glycoprotein known to mediate binding and internalization of IgG-containing targets. FcγRIIA has been observed to translocate into lipids rafts upon binding IgGcontaining targets. We hypothesize that lipid rafts participate to different extents in binding and internalizing targets of different sizes. We demonstrate that disruption of lipid rafts with 8mM methyl-β-cyclodextrin (MβCD) nearly abolishes binding (91% reduction) and phagocytosis (60% reduction) of large IgG-coated targets. Conversely, binding and internalization of small IgGcomplexes is less dependent on lipid rafts (49% and 17% inhibition at 8mM MβCD respectively). These observations suggest that differences between phagocytosis and endocytosis may arise as early as the initial stages of ligand recognition.

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Fc Receptor Phagocytosis

Cited by 2 publications

References 176 publications

Differential kinase requirements in human and mouse Fc-gamma receptor phagocytosis and endocytosis

Differential kinase requirements in human and mouse Fc-gamma receptor phagocytosis and endocytosis

Differential requirement of lipid rafts for FcγRIIA mediated effector activities

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