Aggregated immunoglobulin and Fc fragment of IgG induce IL-6 release from human monocytes

Ling, Zaodung; Ziltener, Hermann J.; Webb, B.; Matheson, David S.

doi:10.1016/0008-8749(90)90189-x

Cited by 43 publications

(25 citation statements)

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“…3). The induction of interleukin-6 production by aggregated (but not monomeric) IgG and Fc fragments may be an additional factor maintaining the baseline level of NK activity in the presence of aggregated IgG and Fc fragments [14].…”

Section: Methodsmentioning

confidence: 99%

Blast transformation of lymphocytes and the activity of natural killer cells in the presence of γ-globulinin vitro

et al. 1994

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1317components increase the sensitivity of platelets to ADP by actively interacting with the cell membrane. This assumption does not contradict the findings of other researchers who demonstrated a stimulatory effect of peptoglycans of nontoxigenic DCB on cultured immune cells in vitro.Thus, this study has shown that diphtheria toxin, diphtheria anatoxin, and codivac are agents that directly affect the functional activity of human platelets. In addition, it was found that diphtheria toxin and anatoxin reduce ADP-induced and total platelet aggregation, the decrease being dependent on preparation dose and incubation time. However, codivac, a glycopeptide from the cell wall of nontoxigenic DCB, stimulates platelet a~gregation in all experimental series.The cytotoxic activity of natural killer cells against 3H-uridine-labeled target cells (human erythromyeloleukosis cells K-562) and the intensity of spontaneous blast transformation are studied in vitro in the presence of human serum T-globulin. It is shown that spontaneous blast transformation is 49-51% due to the presence of aggregated ?-globulin, while the aggregate-free y-globulin fraction does not induce this reaction. The cytotoxic activity of natural killer cells in vitro declines in the presence of native ~,-globulin, which is related to the influence of aggregated y-globulin, the intensity of whose formation may increase upon a manyfold decrease in the y-globulin content of the preparation.

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Section: Methodsmentioning

confidence: 99%

Blast transformation of lymphocytes and the activity of natural killer cells in the presence of γ-globulinin vitro

et al. 1994

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“…Idiotype-antiidiotype interaction and receptor blockade are other possible mechanisms by which IVIG preparations exert their immune modulatory effects in autoimmune disease such as acute idiopathic thrombocytopenic purpura, Kawasaki disease and graft versus host disease [43, 44, 45, 46]. Immune complexes have also been shown to induce the secretion of cytokines such as TNF-α [30, 35], and IL-6 [31] from human monocytes via Fc-receptor interaction. Elevated levels of IL-6 and IL-8 have been reported within 1 h after IVIG infusion [35].…”

Section: Discussionmentioning

confidence: 99%

“…A marked increase in IL-6 production was noted in the presence of LPS/IgG complexes and complement, while TNF-α production was suppressed. There are numerous in vitro experimental reports which suggest that immunoglobulin preparations and immune complexes affect the levels of pro-inflammatory cytokines and other mediators of immune response [26, 28, 29, 30, 31, 32, 33, 34]. Aukrust et al [35] have reported increased plasma levels of IL-6, IL-8, TNF-α and soluble TNF receptors (sTNFR) in 12 patients with primary immunodeficiency (PID) who were infused with an IVIG preparation.…”

Section: Introductionmentioning

confidence: 99%

IVIG Adverse Reactions: Potential Role of Cytokines and Vasoactive Substances

et al. 1998

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Background and Objectives: A clinical study was conducted to determine the effect of IVIG infusion rates on adverse experiences (AE) and on serum levels of cytokines and vasoactive substances. Materials and Methods: Forty-two healthy volunteers were randomized into 3 groups with maximum IVIG infusion rates of 0.04, 0.06, and 0.08 ml/kg/min, and a final dose of 0.5 g IgG/kg body weight. Results: Adverse reactions were noted only at the highest infusion rate of 0.08 ml/kg/min, except in 1 subject infused at 0.06 ml/kg/min. There were significant increases in IL-6 (p = 0.011) and thromboxane B₂ (p = 0.007) in AE subjects as compared to non-AE subjects. Conclusion: IVIG-induced adverse reactions occur more often with rapid infusion rates and may be mediated by elevated levels of inflammatory cytokines and vasoactive substances.

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“…While in most of the previous reports FcγR-triggered cytokine release was induced either by solid-phase bound IgG (Herrmann et al, 1992), complexed IgG (Ling et al, 1990) or IgG-sensitized erythrocytes (Davenport et al, 1994), there is little known about the FcγR-mediated cytokine release induced by anti-tumour antibodies bound to their tumour cell-associated antigens (Wing et al, 1996). This may be of importance in the preclinical evaluation of anti-tumour mAbs.…”

mentioning

confidence: 99%

“…Apart from their function as trigger molecules in antibody-mediated cellular cytolysis (Van de Winkel et al, 1989), both classes of FcγR have been implicated in Fc-dependent stimulation of cytokine release (Debets et al, 1990). Signalling through FcγRs activates human leucocytes to secret various pro-inflammatory cytokines like GM-CSF (Herrmann et al, 1992), interleukin (IL)-6 (Ling et al, 1990) or IL-8 (Marsh et al, 1995).…”

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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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Aggregated immunoglobulin and Fc fragment of IgG induce IL-6 release from human monocytes

Cited by 43 publications

References 28 publications

Blast transformation of lymphocytes and the activity of natural killer cells in the presence of γ-globulinin vitro

Blast transformation of lymphocytes and the activity of natural killer cells in the presence of γ-globulinin vitro

IVIG Adverse Reactions: Potential Role of Cytokines and Vasoactive Substances

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

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