NATURAL KILLER (NK) ACTIVITY OF PERIPHERAL BLOOD AND REGIONAL LYMPH NODES IN PATIENTS WITH GENITOURINARY MALIGNANT TUMORS

Marazuela M, Vargas JA, Alvarez-Mon M, Albarrán F, Lucas T, Durántez A. Impaired natural killer cytotoxicity in peripheral blood mononuclear cells in Graves' disease. Eur J Endocrinol 1995;132:175–80. ISSN 0804–4643 We studied the natural killer (NK) activity of peripheral blood mononuclear cells (PBMC) in patients with Graves' disease (GD). Peripheral blood mononuclear cells from 20 untreated hyperthyroid patients with GD showed a significantly reduced NK activity against 51 Cr-labeled K562 cells (33.9 ± 15.9%), while in 32 euthyroid patients under antithyroid drug therapy, NK activity was similar to that of controls (46.9 ± 17.3 and 49.9 ± 20.2%, respectively). Furthermore, normalization of thyroid function with antithyroid drugs was associated with a significant increase and normalization of NK activity during the follow-up of nine GD patients (from 29.2 ± 17.9 to 48.1 ± 16.5%). This phenomenon could not be ascribed to a defective number of NK cells because the amounts of CD56 + and CD16 + cells in PBMC from both hyperthyroid and euthyroid GD patients were within normal ranges. Natural killer activity of PBMC from patients with toxic multinodular goiter was similar to that of normal controls (45 ± 12.8 to 49.9 ± 20%). No correlation was found between natural killer activity and serum levels of free thyroxine, TSH-inhibitory immunoglobulins, thyroidal antibodies to thryoglobulin and thyroidal microsomal antigen, dose or duration of antithyroid drug therapy. Natural killer activity from both controls and GD patients was enhanced in vitro by addition of recombinant interleukin 2 (IL-2), reaching control levels in hyperthyroid patients. These abnormalities were not associated with a defective IL-2 production by T cells, nor with a decreased IL-2R expression. We conclude that in untreated Graves' disease there is a decrease in NK cell activity in PBMC, probably dependent on the autoimmune process. Possible biological and clinical implications are discussed. Monica Marazuela, Hospital de la Princesa, c/Diego de Léon 62, Madrid 28006, Spain

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Sulphasalazine and Derivatives, Natural Killer Activity and Ulcerative Colitis

Clinical Science ◽

10.1042/cs0690177 ◽

1985 ◽

Vol 69 (2) ◽

pp. 177-184 ◽

Cited By ~ 26

Author(s):

P. R. Gibson ◽

D. P. Jewell

Keyword(s):

Ulcerative Colitis ◽

Natural Killer ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Nk Activity ◽

Aminosalicylic Acid ◽

Lipoxygenase Inhibitor ◽

Peripheral Blood Mononuclear ◽

Killer Activity

1. The effects of sulphasalazine, 5-aminosalicylic acid (5-ASA), sulphapyridine and azodisalicylic acid (ADS) in vitro on the natural killer (NK) activity of peripheral blood mononuclear cells (MNC) have been examined and compared with those of the lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA) and the cyclooxygenase inhibitor, indomethacin. 2. Sulphasalazine, sulphapyridine and ADS inhibited NK activity with 50% inhibitory concentrations (IC50) of 0.7, 2.5 and 4.0 mmol/l respectively. The effect was rapidly reversible. In contrast, 5-ASA minimally inhibited NK activity at 50 mmol/l only. 3. NDGA potently inhibited NK activity (IC50 27 μmol/l) but this was only partly reversible in short term incubations. Indomethacin had no effect at concentrations less than those inhibiting cyclo-oxygenase activity (1-10 μmol/l) but potently and reversibly inhibited NK activity at or above 25 μmol/l. 4. The inhibitory effects observed were unlikely to be due to direct toxicity of effector cells as 5-ASA, sulphapyridine and ADS had no effect on the viability of peripheral blood MNC, whereas NDGA and indomethacin lysed MNC only at maximal concentrations tested. Though sulphasalazine produced MNC lysis at and above 1 mmol/l, the rapid reversibility of the inhibition of NK activity at 1 mmol/l suggested that lysis of NK cells contributed little to the suppressive effect at this concentration. 5. The disparity of the therapeutic efficacy and effects on NK activity of sulphasalazine and its derivatives in vitro may suggest that NK activity is not a major pathogenic mechanism in ulcerative colitis. Any inhibitory effect on cellular immune function of indomethacin does not necessarily reflect an effect of cyclo-oxygenase inhibition.

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Severe deficiency of natural killer activity in the peripheral blood of patients with hairy cell leukemia

Blood ◽

10.1182/blood.v61.6.1132.bloodjournal6161132 ◽

1983 ◽

Vol 61 (6) ◽

pp. 1132-1137 ◽

Cited By ~ 3

Author(s):

LP Ruco ◽

A Procopio ◽

V Maccallini ◽

A Calogero ◽

S Uccini ◽

...

Keyword(s):

Natural Killer ◽

Peripheral Blood ◽

Hairy Cell Leukemia ◽

Nk Activity ◽

Hairy Cell ◽

Cell Leukemia ◽

Neoplastic Cells ◽

Killer Activity ◽

Effector Cells ◽

Low Levels

Natural killer (NK) activity against K-562 tumor cells was evaluated in peripheral blood leukocytes (PBL) obtained from untreated patients affected by hairy cell leukemia (HCL). NK activity present in PBL from 10 HCL patients was at least six-fold lower (p less than 0.01) than that present in PBL from 15 healthy donors. Decreased NK activity in HCL PBL was not due to dilution of the NK effector cells by the neoplastic cells; in fact, NK activity of PBL from 4 HCL patients with less than 5% circulating neoplastic cells was still five-fold lower (p less than 0.01) than that present in normal PBL. Partial characterization of the NK defect in HCL patients indicated that: (A) defective cytotoxicity was not dependent on the duration of the assay; (B) HCL PBL added to normal PBL during the assay did not exert suppressor activity; (C) the NK activity of HCL PBL could be potentiated in vitro by interferon; and (D) low levels of NK activity were associated with reduced numbers of circulating monocytes (p less than 0.01) and of large granular lymphocytes (LGL) (p less than 0.01). In conclusion, our results indicate that the low levels of NK activity present in the peripheral blood of HCL patients may be related to reduced numbers of circulating effector cells.

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Natural killer (NK) activity in peripheral blood lymphocytes of patients with benign and malignant breast disease

British Journal of Cancer ◽

10.1038/bjc.1982.245 ◽

1982 ◽

Vol 46 (4) ◽

pp. 611-616 ◽

Cited By ~ 51

Author(s):

D White ◽

D B Jones ◽

T Cooke ◽

N Kirkham

Keyword(s):

Natural Killer ◽

Peripheral Blood ◽

Breast Disease ◽

Peripheral Blood Lymphocytes ◽

Nk Activity ◽

Blood Lymphocytes ◽

Malignant Breast

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The Krüppel-Like Factor 4 (KLF4) Modulates Survival and Tissue Distribution of Natural Killer Cells.

Blood ◽

10.1182/blood.v114.22.282.282 ◽

2009 ◽

Vol 114 (22) ◽

pp. 282-282

Author(s):

Chun Shik Park ◽

Ping-Hsien Lee ◽

Takeshi Yamada ◽

Maksim Mamonkin ◽

H. Daniel Lacorazza

Keyword(s):

Bone Marrow ◽

T Cells ◽

Lymph Nodes ◽

Nk Cells ◽

Tissue Distribution ◽

Natural Killer ◽

Peripheral Blood ◽

Nk Cell ◽

Wild Type ◽

Deficient Mice

Abstract Abstract 282 Natural Killer (NK) cells are important mediators of the innate immune system that could be targeted therapeutically to treat hematologic malignancies and to prevent graft-versus-host disease. Hence, a better understanding of NK cell survival and tissue trafficking at steady state is vital to develop cell-based therapies. Genes that control proliferation are often involved in tissue distribution of lymphocytes, such as KLF2 in T cells. KLF4, another member of the Krüppel-like factor family, can activate and repress genes involved in diverse cellular processes. We recently reported that KLF4 is part of a novel inhibitory pathway that prevents proliferation of naïve T cells during homeostasis and retain memory T cells in lymph nodes (Yamada et al., Nature Immunology, 2009). In this work, we studied the role of KLF4 in the development and maintenance of NK cells by deleting Klf4-floxed gene (fl/fl) using the Mx1-Cre system. The percentage of NK1.1+TCR- cells is significantly reduced in peripheral blood of Klf4-deficient (▪/▪) mice (fl/fl: 3.4±1.1 versus ▪/▪: 1.2±0.1, n=9) and also absolute numbers in spleen (▪/▪: 1.1±1.3 ×106, n=6) due to increased percentage of Annexin V positive cells (fl/fl: 9.2±3.2 versus ▪/▪: 22.9±15.5, n=15). The number of CD49d+TCR- cells was also significantly reduced in peripheral blood and spleen of Klf4-deficient mice. In contrast, the number of NK cells in bone marrow and lymph nodes of Klf4-deficient mice was similar to controls. Deletion of Klf4 gene led to reduced numbers of NK1.1+TCR-CD27+CD11b+ and NK1.1+TCR-CD27-CD11b+ cells, which correlated with increasing apoptosis of these subsets. Yet, the percentages of these NK cell subsets were normal in bone marrow ruling out a developmental defect in this tissue. Transplant of wild type and Klf4-deficient bone marrow cells into wild type mice suggested environmental rather than cell intrinsic defects. NK cells (NK1.1+TCR-) isolated from spleen of Klf4-deficient mice showed to be functional in a cytotoxicity assay using a mixture of differentially CFSE-labeled RMA-S (target) and EL4 (control). In summary, KLF4 plays a key role in the maintenance of mature NK cells in peripheral blood and spleen. Disclosures: No relevant conflicts of interest to declare.

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Occult metastases of oral cavity cancers

Acta chirurgica iugoslavica ◽

10.2298/aci0401077d ◽

2004 ◽

Vol 51 (1) ◽

pp. 77-81 ◽

Cited By ~ 1

Author(s):

Milovan Dimitrijevic ◽

A. Mikic ◽

Z. Petrovic ◽

Ivica Pendjer ◽

Snezana Jesic ◽

...

Keyword(s):

Oral Cavity ◽

Lymph Nodes ◽

Neck Dissection ◽

Malignant Tumors ◽

Tongue Cancer ◽

Regional Lymph Nodes ◽

Term Survival ◽

Occult Metastases ◽

Floor Of Mouth ◽

Regional Metastases

Despite new approaches to treatment and lower mortality, malignant tumors of the head and neck, including the malignant tumors of the oral cavity, still represent significant oncological problem because long-term survival has not been significantly prolonged. The growth of tumors of this localization is fast and infiltrative. while early metastases of regional lymph nodes are rather frequent. Malignant tumors of the oral cavity account for 1.1% of population in our community (Dimitrijvic, 2001). The objective of the study was to analyze regional metastases of the cancers of the tongue and the floor of mouth in 101 patients with planocellular cancers treated in the period 1991 to 1995.Clinically positive regional lymph nodes were found in 67.3% of patients, while the most commonly involved regions were submandibular (47.4%) and upper jugular region (46.1%). They were more frequent in localization of the floor of mouth than in case of tongue cancer. Three types of neck dissections were used for surgical treatment of patients. In the group of patients with clinically negative results of the neck (NO) who underwent neck dissection, occult metastases of regional lymph nodes were verified pathohistologically in 19.2% of the time. Malignant tumors of the oral cavity are always the indication for neck dissection, even in NO category, on account of high proportion of occult metastases.

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