The serine-threonine mitogen-activated protein kinase (MAPK) family includes extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), and p38 kinases. In NK cells, spontaneous or Ab-mediated recognition of target cells leads to activation of an ERK-2 MAPK-dependent biochemical pathway(s) involved in the regulation of NK cell effector functions. Here we assessed the roles of...

Recent studies of cartilage-hair hypoplasia (CHH), a form of short-limbed dwarfism, have shown that all affected individuals have a cellular proliferation defect that results in a cellular immunodeficiency. However, only a minority of CHH individuals suffer from severe, life-threatening infections. For this reason, relevant immune defense mechanisms that may be responsible for maintaining intac...

Artemisinin, a chemical compound used for the treatment of malaria, has been known to show anti-cancer activity. However, the effect of this chemical on natural killer (NK) cells, which are involved in tumor killing, remains unknown. Here, we demonstrate that artemisinin exerts a potent anti-cancer effect by activating NK cells. NK-92MI cells pre-treated with artemisinin were subjected to a cyt...

The spontaneous natural killer (NK) and lymphokine-activated killer (LAK) cytotoxicity of highly purified CD56+CD3- NK cells (90 to 95%) against NK-sensitive and NK-insensitive target cells was drastically enhanced when a rhamnogalacturonan contained in a commercially available Viscum album extract was present during 4-h cytotoxicity assays. This enhancement correlated strictly with an increase...

Lenalidomide combined with dexamethasone is an effective treatment for refractory/relapsed multiple myeloma (MM). Lenalidomide stimulates natural killer (NK) cells and enhances antitumor responses. We assessed NK cell number and function in 25 patients with MM participating in a clinical trial of lenalidomide and dexamethasone. NK cell numbers increased from a mean of 2.20 ± 0.05 × 10(5)/mL (ba...

Natural killer (NK) cells belong to the innate arm of the immune system and though activated NK cells can modulate immune responses through the secretion of cytokines, their primary effector function is through target cell lysis. Accordingly, cytotoxicity assays are central to studying NK cell function. The 51Chromium release assay, is the "gold standard" for cytotoxicity assay, however, due to...

The CD56 differentiation antigen, recognized by anti-Leu-19 and NKH-1 mAbs, is a 200-220-kD glycoprotein that is expressed predominantly on human NK cells and a minor subset of T lymphocytes mediating MHC-unrestricted cytotoxicity. The recent finding that CD56 is an isoform of the neural cell adhesion molecule (N-CAM) prompted us to examine the adhesive function of CD56 in the NK-target cell in...

Activated NK cells lyse tumor cells and virus-infected cells and produce IFN-gamma upon contact with sensitive target cells. The regulation of these effector responses in resting NK cells is not well understood. We now describe a receptor, KIR2DL4, that has the unique property of inducing IFN-gamma production, but not cytotoxicity, by resting NK cells in the absence of cytokines. In contrast, t...

Physical as well as psychological stress increases the number of circulating peripheral blood NK cells. Whereas some studies found a positive correlation between exercise and NK cell counts and cytotoxic activity, others showed that, for example, heavy training leads to a decrease in per cell NK cytotoxicity. Thus, the impact of exercise on NK cell function and eventually on altered immunocompe...

NK cell-mediated cytotoxicity of target cells is the result of a balance between the activating and inhibitory signals provided by their respective ligand-receptor interactions. In our current study, we have investigated the significance of CD59 on human target cells in modulating this process. A range of CD59 site-specific Abs were used in NK cytotoxicity blocking studies against the CD59-expr...