Impaired natural killer cell function in systemic lupus erythematosus

Sibbitt, Wilmer L.; Likar, Laura L.; Spellman, Craig W.; Bankhurst, Arthur D.

doi:10.1002/art.1780261103

Cited by 33 publications

(8 citation statements)

References 22 publications

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“…Relative NK activity was expressed in LU/107 cells. In some instances, a-IFN (100 unitslml; lnterferon Sciences) was used to pretreat effector cells for 8 hours prior to determination of NK activity in order to quantitate IFN response, as has been previously described (19 Effect of a-IFN on NK cell activity. Because abnormalities in NK cell function in SLE seemed to be related to the presence of serum IFN, the effect of a-IFN on the NK cell activity of normal control PBMC was determined.…”

Section: Methodsmentioning

confidence: 99%

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Relationship between circulating interferon and anti‐interferon antibodies and impaired natural killer cell activity in systemic lupus erythematosus

Sibbitt

Gibbs

Kenny

et al. 1985

Arthritis & Rheumatism

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Interferon (IFN) production and response are impaired in a high percentage of systemic lupus erythematosus (SLE) patients. In addition, elevated serum levels of a-IFN or anti-a-IFN antibodies are present in some SLE patients. This study examined the relationship of circulating IFN and anti-IFN antibodies to the impairment of natural killer (NK) cell function in SLE. All 15 SLE patients studied had measurable circulating a-IFN, while the normal controls had minimal serum IFN. Neither patient nor control sera contained any detectable anti-a-IFN activity. However, most of the SLE patients demonstrated defects in NK cell function. Because these defects in NK cell function appeared to be associated with circulating IFN, but not anti-IFN, antibodies, the effect of prolonged in vitro IFN exposure on NK cell function of peripheral blood qpnonuclear cells was determined. It was found that prolonged exposure to IFN induced both an apparent defect in IFN response and a definite impairment of baseline NK cell function. These results suggest that prolonged elevation of circulating a-IFN levels could be responsible, in part, for the defects in natural cytotoxicity present in SLE.Systemic lupus erythematosus (SLE) is a chronic inflammatory disease characterized by multiFrom

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Section: Methodsmentioning

confidence: 99%

“…Significantly, production of these factors is often impaired in SLE (17,18). However, impaired production of these lymphokines in SLE does not appear to be directly related to dysfunction of the NK cell (19)(20)(21). This suggests that other circulating serum factors may be involved.…”

mentioning

confidence: 99%

Relationship between circulating interferon and anti‐interferon antibodies and impaired natural killer cell activity in systemic lupus erythematosus

Sibbitt

Gibbs

Kenny

et al. 1985

Arthritis & Rheumatism

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“…The percentage of target cells with NK cells bound [26] was determined for three effector cell/target cell ratios: 25:1, 12.5:1, and 1:1. A total of 2.5 !…”

Section: Conjugation Of Nk Cells To Target Cellsmentioning

confidence: 99%

Lysophosphatidylcholine and Arachidonic Acid Are Required in the Cytotoxic Response of Human Natural Killer Cells to Tumor Target Cells

Whalen¹,

Doshi²,

Bader³

et al. 1999

Cell Physiol Biochem

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Treatment of human natural killer (NK) cells with phospholipase A₂ (PLA₂) inhibitors, mepacrine and 4-bromophenacyl bromide (BPB), diminished their ability to lyse K562 target cells by as much as 100%. The ability of NK cells to bind to K562 cells was significantly affected by BPB above 2 μM, but not by mepacrine at any concentration tested. This indicates that BPB is having effects on NK cells unrelated to its inhibition of PLA₂ activity at concentrations above 2 μM. The activation of phospholipase C in response to K562 cell binding (as measured by inositol phosphate turnover) was unaffected by inhibition of the PLA₂ activity. The products of PLA₂ catabolism are a fatty acid (often arachidonic acid) and a lysophospholipid. Inhibition of NK cytotoxicity by mepacrine or BPB is reversed significantly when lysophosphatidylcholine, but no other lysolipid, is added back to the NK cells before assaying for cytotoxicity. Arachidonic acid, but not linoleic acid, also significantly reverses inhibition of NK cytotoxicity. Finally, the 15-lipoxygenase product, 15S-hydroperoxyeicosatetraenoic acid (15S-HPETE), is also able to reverse mepacrine-induced inhibition of NK cytotoxicity. The 5-lipoxygenase product 5S-HPETE was not effective. These data indicate that PLA₂ activation is a necessary signal in human NK cytotoxicity and that it is not involved in protein tyrosine kinase and subsequent phospholipase C activation; these latter two enzymes are also required in the cytotoxic response. Thus PLA₂ activation is either a more distal signal, dependent on activation of some earlier signal, or an independent cosignal stimulated by tumor-target binding which generates lysophosphatidylcholine, arachidonic acid, and/or a lipoxygenase product(s).

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“…The percentage of target cells with bound lympho cytes was determined for three E:T ratios, namely 25:1, 12.5:1 and 1:1 [20]. A total of 25,000 target cells was incubated with the appropriate number of effector cells in HBSS/0.5% gelatin containing either 4.4 m.V/ D-glucosc or 44 mM £>-glucose in the well of a roundbottomed microtiter plate (total incubation volume 210 pi).…”

Section: Conjugation Ofnk Cells To Target Cellsmentioning

confidence: 99%

Inhibition of Human Natural Killer Cell Function in vitro by Glucose Concentrations Seen in Poorly Controlled Diabetes

Whalen¹

1997

Cell Physiol Biochem

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Type 1 and type 2 diabetes mellitus are associated with an increased risk of viral infections and certain tumors. Natural killer (NK) cells appear to have a central role in the immune defense against viral infection as well as tumor cells, and impairment of NK function could result in an increased incidence of infection or tumors. We show that exposure of NK cells to elevated glucose concentrations (in the range seen in poorly controlled diabetes) results in a significant inhibition of their cytolytic function. When glucose is elevated to 44 mM (800 mg/dl), there is a 59% decrease in NK cytolytic function compared to that seen when glucose is in the normal range (4.4-5.5 mM). Specific lysis is inhibited by 42% by 33 mM glucose, and 22 mM glucose produce a 31 % inhibition of specific lysis. This inhibition is not due to a disruption of NK cell binding to target cells. The effect is reversible under the in vitro conditions used, indicating that it is not due to the glycation of proteins that can occur with elevated glucose levels. Exposure of NK cells to 44 mM glucose results in a significant elevation of cAMP, indicating that elevation of this potent inhibitor of NK cytolysis may be in part responsible for the glucose-induced inhibition of NK function.

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Impaired natural killer cell function in systemic lupus erythematosus

Cited by 33 publications

References 22 publications

Relationship between circulating interferon and anti‐interferon antibodies and impaired natural killer cell activity in systemic lupus erythematosus

Relationship between circulating interferon and anti‐interferon antibodies and impaired natural killer cell activity in systemic lupus erythematosus

Lysophosphatidylcholine and Arachidonic Acid Are Required in the Cytotoxic Response of Human Natural Killer Cells to Tumor Target Cells

Inhibition of Human Natural Killer Cell Function in vitro by Glucose Concentrations Seen in Poorly Controlled Diabetes

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