Signal transduction by Fc gamma RIII (CD16) is mediated through the gamma chain.

Wirthmueller, Urs; Kurosaki, Tomohiro; Murakami, Matsuka; Ravetch, Jeffrey V.

doi:10.1084/jem.175.5.1381

Cited by 167 publications

(97 citation statements)

References 46 publications

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“…The functional CD16 receptor consists of two subunits: an ␣ subunit that spans the membrane and functions in binding antigen, and a ␥ subunit (FcRI␥) necessary for receptor assembly and signal transduction (22). Importantly, CD16 binding is preferential for small IgG dimer or trimer complexes that include IgG-anti-IgG antibody complexes, an important component of rheumatoid factors that are potential triggers for onset or maintenance of RA (23)(24)(25)(26).…”

Section: Conclusion Estrogen Can Modulate Proinflammatory Cytokine Rmentioning

confidence: 99%

17β‐estradiol regulates cytokine release through modulation of CD16 expression in monocytes and monocyte‐derived macrophages

Kramer¹,

Krämer²,

Guan³

2004

Arthritis & Rheumatism

174

127

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Objective. Macrophages release cytokines, such as tumor necrosis factor ␣ (TNF␣), interleukin-1 (IL-1), and IL-6, which modulate the symptoms of rheumatoid arthritis (RA). Macrophage release of these cytokines can be modulated by estrogen. Fc␥ receptor type IIIA (CD16a) is a receptor expressed on macrophages that selectively binds IgG molecules, an important rheumatoid factor in RA. Binding of CD16 by anti-CD16 monoclonal antibodies stimulates macrophage cytokine release. We undertook this study to test the hypothesis that decreased concentrations of estrogen (17␤-estradiol) directly cause an increase in CD16 expression, resulting in increased release of proinflammatory cytokines from monocytes and/or macrophages upon receptor binding.Methods. THP-1 cells and female human primary monocytes and monocyte-derived macrophages were treated with no 17␤-estradiol, physiologic levels (1 ؋ 10 ؊8 M) of 17␤-estradiol, or 1 ؋ 10 ؊8 M 17␤-estradiol followed by withdrawal of 17␤-estradiol. Surface expression of CD16 and CD16 messenger RNA was measured using fluorescence-activated cell sorting (FACS) and semiquantitative reverse transcription-polymerase chain reaction, respectively. Cytokine release from 17␤-estradiol-treated or untreated monocytes was then quantitated by enzyme-linked immunosorbent assay and FACS after crosslinking the receptor with anti-CD16 antibodies.Results. CD16 transcript significantly increased in macrophage-like THP-1 cells and in primary, peripheral blood macrophages in the absence of 17␤-estradiol, and the observed increase in message was dependent on transcription. CD16 receptor levels on CD14؉, transforming growth factor ␤-treated primary monocytes also increased in cells deprived of 17␤-estradiol. Analysis of the cytokines released showed that CD16 crosslinking stimulated significant increases in TNF␣, IL-1␤, and IL-6 due to the absence of estrogen.Conclusion. Estrogen can modulate proinflammatory cytokine release from activated monocytes and/or macrophages, in part through modulation of CD16 expression.

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Section: Conclusion Estrogen Can Modulate Proinflammatory Cytokine Rmentioning

confidence: 99%

17β‐estradiol regulates cytokine release through modulation of CD16 expression in monocytes and monocyte‐derived macrophages

Kramer¹,

Krämer²,

Guan³

2004

Arthritis & Rheumatism

174

127

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“…Murine neutrophils express polypeptide-anchored CD16A and CD32B (11), whereas human neutrophils express GPI-anchored CD16B and polypeptide-anchored CD32A (12,13). The CD16A expressed on mouse neutrophils can deliver the activation signal by associating with ITAM-containing ␥ or subunits (14), and this activation can be regulated by ITIM-containing mouse CD32B (15). In contrast, human CD32A has an ITAM motif in the cytoplasmic domain and is capable of transducing inflammatory signals (16,17).…”

mentioning

confidence: 99%

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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“…NK cells express multiple ITAM signaling chains, including KARAP/DAP12, CD3, and Fc⑀RI␥ (8). Ly-49D and Ly-49H associate with KARAP/DAP12 (21,22), NKR-P1 associates with Fc⑀RI␥ (23), and CD16 associates with CD3 (24,25) and Fc⑀RI␥ (26). Although it is not yet known whether these signaling chains are functionally equivalent, when activating receptors are cross-linked, the ITAMs in the associated signaling chain become tyrosine phosphorylated.…”

mentioning

confidence: 99%

Costimulation of Multiple NK Cell Activation Receptors by NKG2D

Carayannopoulos

Poursine-Laurent

et al. 2002

The Journal of Immunology

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The activation of NK cells is mediated through specific interactions between activation receptors and their respective ligands. Little is known, however, about whether costimulation, which has been well characterized for T cell activation, occurs in NK cells. To study the function of NKG2D, a potential NK costimulatory receptor, we have generated two novel hamster mAbs that recognize mouse NKG2D. FACS analyses demonstrate that mouse NKG2D is expressed on all C57BL/6 IL-2-activated NK (lymphokine-activated killer (LAK)) cells, all splenic and liver NK cells, and ∼50% of splenic NKT cells. Consistent with limited polymorphism of NKG2D, its sequence is highly conserved, and the anti-NKG2D mAbs react with NK cells from a large number of different mouse strains. In chromium release assays, we show that stimulation of NK cells with anti-NKG2D mAb can redirect lysis. Also, enhanced lysis of transfected tumor targets expressing NKG2D ligand could be inhibited by addition of anti-NKG2D mAb. Interestingly, stimulation of LAK cells via NKG2D alone does not lead to cytokine release. However, stimulation of LAK via both an NK activation receptor (e.g., CD16, NK1.1, or Ly-49D) and NKG2D leads to augmentation of cytokine release compared with stimulation through the activation receptor alone. These results demonstrate that NKG2D has the ability to costimulate multiple NK activation receptors.

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Signal transduction by Fc gamma RIII (CD16) is mediated through the gamma chain.

Cited by 167 publications

References 46 publications

17β‐estradiol regulates cytokine release through modulation of CD16 expression in monocytes and monocyte‐derived macrophages

17β‐estradiol regulates cytokine release through modulation of CD16 expression in monocytes and monocyte‐derived macrophages

Signal-Specific Activation and Regulation of Human Neutrophil Fcγ Receptors

Costimulation of Multiple NK Cell Activation Receptors by NKG2D

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