Effect of 4-hydroxynonenal, a product of lipid peroxidation, on NK susceptibility of human K562 target cells.
4-Hydroxynonenal (HNE) is one of the major breakdown products generated by lipid peroxidation of cellular membranes. The level of lipid peroxidation and the concentration of its products are inversely related to the rate of cell proliferation and directly related to the level of cell differentiation. It has been reported that HNE inhibits DNA synthesis, ornithine decarboxylase (ODC) activity and c-myc expression in different leukemic cells lines. It has also been demonstrated that HNE inhibits proliferation and induces differentiation in HL60 cell line. In the present study the effects of HNE, at concentrations close to those found in the normal tissues, on the NK susceptibility of human K562 target cells were analyzed. Repeated treatments at 45 minutes intervals with 1 microM HNE were performed to maintain the cells in the presence of the aldehyde for 12 hours. The effect of HNE was compared with that obtained in Haemin-treated cells. HNE causes a strong inhibition of cells growth (53% vs. 34% with Haemin) without affecting cell viability. We further investigated the NK susceptibility of K562 cell line upon in vitro treatment with HNE. Cytotoxic activity of mononuclear cells (MNC) from peripheral blood of healthy donors was determined by 4 hours Cr51-release assay. The results obtained, expressed in terms of percentage of specific lysis at different E:T ratios and in terms of KC (10(6)) at the E:T ratio of 50:1, show that HNE treatment of K562 cells leads to a marked reduction of susceptibility to NK cells; this decrease is very close to that found in the K562 cells treated with Haemin used as inducer. Similar results were obtained using MNC pre-treated with beta-interferon (IFN) as effector cells. MNC show a reduced capacity to lyse HNE-treated cells also under the enhancing cytolytic effect of IFN. These results are in line with data obtained with several common inducers of differentiation such as DMSO, retinoic acid or others.
Rinaldi
M
M
Istituto Medicina Sperimentale, CNR, Area di Ricerca Tor Vergata, Rome, Italy.
Tricarico
M
M
Bonmassar
E
E
Parrella
P
P
Barrera
G
G
Fazio
V M
VM
D000447:Aldehydes / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007167:Immunotherapy; D007372:Interferons / Q000494:pharmacology; D020014:K562 Cells / Q000187:drug effects / Q000276:immunology; D015979:Killer Cells, Lymphokine-Activated; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*
D000447:Aldehydes; D015853:Cysteine Proteinase Inhibitors; D007372:Interferons; C027576:4-hydroxy-2-nonenal