Fc gamma receptor IIIb enhances Fc gamma receptor IIa function in an oxidant-dependent and allele-sensitive manner.

Salmon, Jane E.; Millard, S. Sean; Brogle, N L; Kimberly, Robert P.

doi:10.1172/jci117994

Cited by 114 publications

(69 citation statements)

References 59 publications

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“…PMA-mediated inactivation of Fc␥Rs in this report contradicts a previous report showing that PDBu, another phorbol ester (33), activated the ligand-binding function of CD32A. This difference could be due to the use of different phorbol esters.…”

Section: Specificity Of Pma-mediated Loss In Fc␥rs Ligand-binding Funcontrasting

confidence: 99%

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Signal-Specific Activation and Regulation of Human Neutrophil Fcγ Receptors

Nagarajan

Fifadara

Selvaraj

2005

The Journal of Immunology

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FcγRs with the ITIM domain have been shown to regulate the inflammatory signal delivered by the ITAM-containing FcγRs. In this study, we demonstrate that the function of human neutrophil FcγR type IIA (CD32A) is regulated in a distinct manner by different cell activation signals at the ligand-binding stage. Activation of neutrophils with fMLP up-regulated the ligand-binding function of CD32A, whereas PMA-mediated activation completely abolished ligand binding without altering CD32A expression. Furthermore, PMA treatment also abolished CD16B-dependent ligand binding irrespective of the level of expression. The effect of PMA was cell type specific, because the ligand-binding function of CD32A expressed on cultured cells such as K562 and CHO-CD32A transfectants was not affected by PMA. Interestingly, phorbol 12,13-dibutyrate, another phorbol ester, and IL-8 up-regulated CD32A-dependent ligand-binding function. These results demonstrate that regulation of CD32A-dependent ligand binding in human neutrophils is not only cell type specific but also activation signal specific. Moreover, these results suggest the possibility that signals delivered to neutrophils by various inflammatory stimuli can exert opposing effects on the function of human FcγRs, representing a novel inside-out regulatory mechanism of FcγR ligand binding.

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Section: Specificity Of Pma-mediated Loss In Fc␥rs Ligand-binding Funcontrasting

confidence: 99%

“…An earlier study (33) and findings from this study show that PDBu, in contrast to PMA, up-regulated CD32A-dependent ligand-binding function. Although these two phorbol esters have been shown to transduce similar signals in many cell types, differences in their action on neutrophils have been reported (49,50).…”

Section: Discussionsupporting

confidence: 65%

Signal-Specific Activation and Regulation of Human Neutrophil Fcγ Receptors

Nagarajan

Fifadara

Selvaraj

2005

The Journal of Immunology

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“…Donors homozygous for the NA1 allele of Fc␥RIIIb display a quantitatively greater Fc␥R-dependent phagocytic capacity (17) and greater Fc␥RIIIb enhancement of Fc␥RIIa-specific phagocytosis relative to NA2-homozygous donors (19). To test whether the NA1 allele might have a greater capacity to mobilize azurophilic granules relative to the NA2 allele, we assessed the influence of Fc␥RIIIb-NA1/NA2 polymorphism on the quantitative magnitude of release of ␣-defensins in response to heterotypic cross-linking of Fc␥RIIa and Fc␥RIIIb on TNF-␣-primed neutrophils.…”

Section: Fc␥r-mediated Release Of ␣-Defensins From Neutrophils Is Fc␥mentioning

confidence: 99%

“…Human neutrophils express two structurally distinct Fc␥R, Fc␥RIIa and Fc␥RIIIb (14). Both of these receptors are functionally polymorphic with the H131/R131 single-nucleotide polymorphism of Fc␥RIIa altering the binding of hIgG 2 (15) and mIgG1 (16) and the NA1/NA2 single-nucleotide polymorphisms of Fc␥RIIIb altering the quantitative functional capacity of the receptor (17)(18)(19). ANCA have been shown to engage both neutrophil Fc␥R upon binding to cell-associated ANCA-target Ag with preferential engagement of Fc␥RIIIb presumably due to its numeric predominance over Fc␥RIIa (20 -22).…”

mentioning

confidence: 99%

FcγRIIIb Allele-Sensitive Release of α-Defensins: Anti-Neutrophil Cytoplasmic Antibody-Induced Release of Chemotaxins

Tanaka

Edberg

Chatham

et al. 2003

The Journal of Immunology

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Antineutrophil cytoplasmic Abs (ANCA) can activate neutrophils in an FcγR-dependent manner, but the link between this ANCA-induced effect and mononuclear cell activation with the characteristic granuloma formation of Wegener’s granulomatosis is unclear. Human α-defensins, small cationic antimicrobial peptides, are found in neutrophils and have chemotactic activity for T cells, dendritic cells, and monocytes. In this study, we quantitated the release of α-defensins (human neutrophil peptides 1–3) from human neutrophils after targeted FcγR cross-linking (XL). Homotypic XL of FcγRIIa, FcγRIIIb, or heterotypic XL of both receptors resulted in significant release of α-defensins, an effect also induced by both human polyclonal and murine monoclonal cytoplasmic staining ANCA (anti-proteinase 3). This release of α-defensins, as well as of other granule constituents (ANCA targets anti-proteinase 3 and myeloperoxidase and elastase), was significantly greater in donors homozygous for the NA1 allele of FcγRIIIb than in donors homozygous for NA2. Interestingly, the ANCA-induced release was completely inhibited by the IgG Fc-binding peptide TG19320, which blocks the IgG-Fc region from binding to FcγR. Based on their chemotactic properties, α-defensins and their release by ANCA may contribute to modulation of the acquired immune response and to granuloma formation. The greater activity of the FcγRIIIB-NA1 genotype may also explain the greater severity of disease and its flare-ups in patients with this allele.

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“…However, with increased concentration of sensitizing mAb and subsequently, with an increased formation of a multivalent array of aggregated mAbs on the target cell surface, anti-LeY mAbs may additionally interact with FcγRII. It remains to be shown whether these effects might be related to a heterotypic cluster formation of both FcγR subtypes (Vossebeld et al, 1995), or due to the release of endogenous factors which have been shown to contribute to an up-regulation of FcγRII activity (Trevani et al, 1994;Salmon et al, 1995).…”

Section: mentioning

confidence: 99%

Different types of FC γ -receptors are involved in anti-Lewis Y antibody induced effector functions in vitro

Dettke

Loibner

2000

Br J Cancer

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Summary Stimulation of monocytes by interaction of monoclonal antibodies (mAbs) with Fc gamma receptors (FcγRs) results in the activation of various monocyte effector functions. In the present investigation we show that the anti-Lewis Y (LeY) anti-tumour mAb ABL 364 and its mouse/human IgG1 chimaera induce both antibody-dependent cellular cytotoxicity (ADCC) and the release of tumour necrosis factor α (TNF-α) during mixed culture of monocytes with LeY + SKBR5 breast cancer cells in vitro. Although anti-LeY mAb-mediated TNF-α release paralleled ADCC activity, cytokine release required a higher concentration of sensitizing mAb than the induction of cytolysis. The determination of the FcγR classes involved in the induction of the distinct effector functions showed that anti-LeY mAb-induced cytolysis was triggered by interaction between anti-LeY mAbs and FcγRI. In contrast, mAb-induced TNF-α release mainly depended on the activation of monocyte FcγRII. Neutralization of TNF-α showed no influence on monocyte ADCC activity towards SKBR5 target cells. Our data indicate an independent regulation of anti-LeY mAb induced effector functions of ADCC and TNF-α release which seemed to be triggered by activation of different types of FcγR. © 2000 Cancer Research CampaignKeywords: monocytes; anti-LeY antibody; FcγR; ADCC; TNF-α 441British Journal of Cancer (2000) 82(2), 441-445 © 2000 Cancer Research Campaign Article no. bjoc.1999 Received 4 January 1999 Revised 26 July 1999 Accepted 2 August 1999Correspondence to: M Dettke, Clinic for Blood Group Serology and Transfusion Medicine, AKH Wien, Währinger Gürtel 18-20, A-1090 Vienna, Austria residual lipopolysaccharide (LPS), 10 µg ml -1 polymyxin B was added to the culture medium (Sigma, USA). Tumour cell lineThe human breast cancer cell line SKBR5 was used as LeY + target cells. The cell line was obtained from the Wistar Institute (Philadelphia, PA, USA). Preparation of SKBR5 membrane vesiclesMembrane vesicles of SKBR5 tumour cells were prepared according to the method described (Thom et al, 1977). For removal of membrane-bound glycodeterminants, the membrane preparation was sequentially digested with N-specific glycosidase (N-glycosidase F), neuraminidase (acylneuraminyl hydrolase) followed by endo-α-N-acetylgalactosaminidase to hydrolyse Olinked oligosaccharides (all enzymes from Genzyme, USA). For control, a LeY-bearing neoglycoprotein (LeY-BSA conjugate) was used (Chembiomed, Canada). Enzyme-induced hydrolysis of ABL 364-reactive LeY epitopes was monitored by enzyme-linked immunosorbent assay (ELISA). Unmodified membrane vesicles, enzyme-treated vesicles and controls (LeY-BSA, enzyme-treated LeY-BSA) were coated on microtitre plates. Following incubation with mAb ABL 364, bound ABL 364 was detected by horseradish peroxidase-conjugated goat anti-mouse IgG3 (Southern Biotechnology, UK). Compared to unmodified membrane vesicles enzyme treatment reduced the presence of ABL364-reactive LeY epitopes on the membrane preparation by 80% (data not shown). In vitro ADCC assayAnti-LeY ...

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Fc gamma receptor IIIb enhances Fc gamma receptor IIa function in an oxidant-dependent and allele-sensitive manner.

Abstract: Introduction (9). In contrast to these systems, signaling through the T cell receptor upregulates the avidity of CD2 for CD58 (LFA-1) through inside-out signaling requiring specific domains of the CD2 cytoplasmic tail (10,11

Cited by 114 publications

References 59 publications

Signal-Specific Activation and Regulation of Human Neutrophil Fcγ Receptors

Signal-Specific Activation and Regulation of Human Neutrophil Fcγ Receptors

FcγRIIIb Allele-Sensitive Release of α-Defensins: Anti-Neutrophil Cytoplasmic Antibody-Induced Release of Chemotaxins

Different types of FC γ -receptors are involved in anti-Lewis Y antibody induced effector functions in vitro

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