Natural Killer Activity Of Human Lymphocytes Research Articles

The by-products generated during sarin synthesis in the Tokyo sarin disaster induced inhibition of natural killer and cytotoxic T lymphocyte activity

More than 5000 passengers on Tokyo subway trains were injured by the nerve gas, sarin and its by-products. Analysis of phosphor-carrying metabolites of sarin and its by-products in urine samples from the victims suggested that they were exposed not only to sarin, but also by-products generated during sarin synthesis, i.e. diisopropyl methylphosphonate (DIMP) and diethyl methylphosphonate (DEMP). We suspected genetic after-effects due to sarin by-products, thus, we checked the frequency of sister chromatid exchange (SCE) and found that SCE was significantly higher in the victims than in a control group, and that DIMP and DEMP significantly induced human lymphocyte SCE in vitro. In the present study, to explore whether DIMP and DEMP, which induced a high frequency of SCE of lymphocytes, also affected the lymphocyte functions, we examined the effect of DIMP and DEMP on splenic natural killer (NK) and splenic cytotoxic T lymphocyte (CTL) activity in mice, and NK activity of human lymphocytes in vitro. We found that DIMP and DEMP significantly inhibited NK and CTL activity in a dose-dependent manner. The inhibition induced by DIMP was stronger than that by DEMP. The effect of DIMP and DEMP on the splenic NK activity of mice was stronger than on the splenic CTL activity, and the human lymphocytes is more sensitive to DIMP and DEMP than the splenocytes of mice.

Melatonin-induced suppression of human lymphocyte natural killer activity in vitro.

One of the important immune functions influenced by neuroendocrine factors is natural killer (NK) activity, which is directed against neoplastic and virus-infected cells. The effects of melatonin (Mel) and N-acetylserotonin (NAc-5HT) on NK activity of human peripheral blood lymphocytes were investigated. Leukocytes of healthy human subjects were used in the experiment. NK activity was estimated by measurement of radioactive chromium (51Cr) release from human leukemia cells K 562 (target cells). The previous exposure of human lymphocytes (effector cells) to Mel in concentrations of 10(-6) M and 10(-10) M resulted in an inhibition of NK activity (P less than 0.01) for all the examined effector-target cell ratios (10:1; 20:1, 40:1). NK activity was also suppressed by Mel (10(-8) M), but only if effector-target ratio equal to 20:1 was used (P less than 0.02), and by Mel (10(-12) M) for effector-target ratio equal to 40:1 (P less than 0.05). In none of the examined concentrations did NAc-5HT inhibit NK activity of human lymphocytes. On the basis of the data reported above, a direct suppressive effect of Mel (but not of NAc-5HT) on NK activity of human peripheral blood lymphocytes can be assumed.

Enhancement of human lymphocyte natural killer activity by somatostatin

The effect of somatostatin 1–14 (SS) on the natural killer (NK) activity of human peripheral blood lymphocytes was investigated. The NK activity was estimated by means of radioactive chromium ( 51Cr) assay with the use of human leukemia cells K 562 as targets. The previous exposure of lymphocytes obtained from healthy donors to somatostatin in the concentration of 10 −8 and 10 −6 M resulted in the enhancement of NK activity. The finding provides a further evidence of the immunomodulating somatostatin action.

Effects of two neuropeptides, somatoliberin (GRF) and corticoliberin (CRF), on human lymphocyte natural killer activity

The effect of corticoliberin (CRF) and somatoliberin (GRF) on the natural killer (NK) activity of human peripheral blood lymphocytes was investigated. NK activity was estimated by means of the radioactive chromium ( 51Cr) assay in which human leukemia K 562 cells serve as targets. Exposure of human lymphocytes (effector cells) to 10 −6 to 10 −10 M concentrations of CRF inhibited NK activity. NK activity was also suppressed by the same concentrations of GRF, but only when an effector:target cell ratio of 40:1 was used. In contrast, at effector:target ratios of 20:1 and 10:1, stimulatory effects of GRF were observed.