NEGATIVE REGULATION OF HUMAN NK ACTIVITY BY MONOMERIC IgG

Sulica, Andrei; Gherman, M; Manciulea, Moiara; Galatiuc, Cecilia; Herberman, Ronald B.

doi:10.1016/b978-0-12-341360-4.50098-6

Cited by 4 publications

(6 citation statements)

References 19 publications

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“…We previously demonstrated that short-term interactions (1-2 h) of mIgG, its Fc fragment or a synthetic peptide with FcyRIIIA inhibited NK activity [8,91, in contrast to stimulation induced by antLCD16 mAb [5,7,121. Thus, monovalent ligands of FcyRIIIA had an opposite effect on NK activity from that mediated by antLCD16 mAb [5,7,121.…”

Section: Discussionmentioning

confidence: 99%

“…The Fc fragments of human IgG were produced as described [8]. Human recombinant IL-2, a gift from Chiron Corp., Emeryville, CA, was used at a concentration range of 600-6000 IU/ml (2.2-22.2 nM; lIU=3.7pM).…”

Section: Biological Reagentsmentioning

confidence: 99%

“…K562 and Daudi targets labeled with "Cr were used to measure NK activity and lymphokine-activated killing (LAK), respectively, as described [8]. Specific cytotoxicity was determined at various effector: target (E : T) ratios, and lytic units (LU) were calculated.…”

Section: Cytotoxicity Assaysmentioning

confidence: 99%

“…Human mIgG was isolated from intravenous IgG (Gamimmune N, Cutter Biologicals, Elkhart, IN) as described [8,91 or by gel filtration on Sephacryl S300 (Pharmacia, Uppsala, Sweden). The Fc fragments of human IgG were produced as described [8].…”

Section: Biological Reagentsmentioning

confidence: 99%

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Divergent effects of FcγRIIIA ligands on the functional activities of human natural killer cells in vitro

Sulica¹,

Metes²,

Gherman³

et al. 1996

Eur J Immunol

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The Fc gamma receptor (R)IIIA (CD 16) plays an important role in regulating the cytotoxic and non-cytotoxic functions of human natural killer (NK) cells. Some anti-CD 16 monoclonal antibodies (mAb) have been shown to stimulate NK activity, while human monomeric (m) IgG induces dose-dependent inhibition of NK activity. To explore further these interactions mediated via Fc gamma RIIIA, purified NK cells were cultured for 2-3 days in the presence of mIgG, 3G8 mAb, interleukin-2 (IL-2) or a combination of mIgG or 3G8 with IL-2. Binding of mIgG or 3G8 to Fc gamma RIIIA induced divergent effects of functions of cultured NK cells: 3G8 mAb + IL-2 induced dose-dependent inhibition of proliferation attributable to apoptosis; in contrast, mIgG + IL-2 significantly increased NK cell proliferation. Incubation of NK cells in the presence of mIgG up-regulated expression of surface activation markers (CD69, IL-2R alpha, ICAM-1), cytotoxicity, cytokine production (IL-1 beta, IFN-gamma and TNF-alpha) and release of soluble IL-2R. Thus, mIgG binding to Fc gamma RIIIA induced stimulatory signals in human NK cells, leading to up-regulation of IL-2R alpha expression, cell proliferation and cytokine release.

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Section: Discussionmentioning

confidence: 99%

Section: Biological Reagentsmentioning

confidence: 99%

Section: Cytotoxicity Assaysmentioning

confidence: 99%

Section: Biological Reagentsmentioning

confidence: 99%

See 2 more Smart Citations

Divergent effects of FcγRIIIA ligands on the functional activities of human natural killer cells in vitro

Sulica¹,

Metes²,

Gherman³

et al. 1996

Eur J Immunol

Self Cite

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“…NK activity is inhibited by aggregated IgG (Saksela et al, 1979) or immune complexes (Memll et al, 1981). In addition, monomeric IgG or its Fc fragments down-regulate NK activity (Sulica et al, 1982). Down-regulation of NK activity is not related to steric hindrance of binding to the target cells, but rather to events prior to effector-celvtarget-cell interaction (Merrill et al, 1982).…”

Section: Hpgpc Fraction Numbermentioning

confidence: 99%

Humoral modulation of lymphokine‐activated killer (LAK)‐cell induction in humans: IgG‐related and non‐IgG inhibitors in sera from cancer patients

Riley

Pellis

Schantz

et al. 1990

Intl Journal of Cancer

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Soluble inhibitors of lymphokine-activated killer (LAK) cell induction were characterized and purified from serous fluids from healthy donors or from patients with advanced cancer. Inhibitory activity in sera from cancer patients was partially absorbed with protein A agarose or anti-human IgG agarose. Following absorption, residual inhibition varied with individual sera, suggesting the presence of IgG-related and non-IgG inhibitory factors, and the proportions varied in the patient population. IgG, purified by affinity chromatography from ascitic fluids, from plasma of cancer patients, and from plasma of healthy donors, significantly inhibited IL-2 induction of LAK cells in a dose-dependent manner. Irrespective of the sources, inhibitory activity resided in the high-molecular-weight IgG fraction composed of IgG aggregates and immune complexes, but not monomeric IgG. Commercially prepared human IgG in aggregated form, but not in monomeric form, inhibited LAK cell induction in a dose-dependent manner. In contrast, neither bovine IgG nor human albumin affected LAK cell induction, even at higher concentrations. Aggregated human IgG inhibited LAK cell induction in unfractionated peripheral blood mononuclear cells (PBMC) but not in monocyte-depleted peripheral blood lymphocytes (PBL). Despite extensive (greater than 99%) depletion of IgG by protein-G affinity chromatography, the serous fluid from cancer patients displayed significant inhibitory activity. Fractionation of the IgG-depleted inhibitory materials by Sephacryl S-300, high-pressure ion-exchange column (HPIEC) or gel-permeation chromatography (HPGPC) demonstrated a 65-kDa inhibitor, distinct from IgG. Affigel-blue affinity chromatography of the 65-kDa fraction depleted albumin but did not remove the inhibitory activity, suggesting that the 65-kDa inhibitor is not serum albumin nor an albumin-bound component. These results suggest that serous fluids from patients with advanced-stage cancer contain 2 distinct regulators for LAK cell induction: (I) aggregated IgG and (2) a 65-kDa inhibitor, distinct from albumin.

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Antitumour Lymphocyte Responses

Rees¹,

Ali²

1985

Immunological Aspects of Cancer

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NEGATIVE REGULATION OF HUMAN NK ACTIVITY BY MONOMERIC IgG

Cited by 4 publications

References 19 publications

Divergent effects of FcγRIIIA ligands on the functional activities of human natural killer cells in vitro

Divergent effects of FcγRIIIA ligands on the functional activities of human natural killer cells in vitro

Humoral modulation of lymphokine‐activated killer (LAK)‐cell induction in humans: IgG‐related and non‐IgG inhibitors in sera from cancer patients

Antitumour Lymphocyte Responses

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