Noncytotoxic alkyl-lysophospholipid treatment increases sensitivity of leukemic K562 cells to lysis by natural killer (NK) cells.
Alkyl-lysophospholipids (ALP) are a group of anti-cancer compounds tha t have previously been shown to have the unique feature of being selectively toxic to neoplastic tissues. Because alkyl-lysophospholipids target the cell membrane as their site of action, our aim was to analyse the immunological effects of a nonlethal ALP treatment on leukemic K562 cells. In this in vitro study we used ET-18-OCH3, one of the most potent ALP derivatives, at different concentrations ranging from 25 up to 100 microgram/ml. By measurement of cell viability and of apoptosis, we determined a concentration of 25 microgram/ml ET-18-OCH3 and an incubation period of 2 hr as nonlethal for K562 cells; higher concentrations markedly reduced cell viability and led to induction of apoptosis. Similar to the effects induced by nonlethal heat shock, a nontoxic ET-18-OCH3 treatment led to a significant increase in the sensitivity of K562 cells to lysis by interleukin-2 (IL-2) stimulated natural killer (NK) cells. With respect to these results, we investigated the influence of nonlethal ALP treatment on the cell surface expression patterns and compared it to the results obtained with nonlethal heat shock. ALP treatment does not induce major histocompatibility complex (MHC) expression; however, a significant increase in the cell surface expression of HSP72 was shown by immunoblot analysis of membrane lysates of either untreated or ET-18-OCH3 treated K562 cells. The increased sensitivity of ET-18-OCH3 treated K562 cells to lysis by NK cells could be correlated with the elevated cell surface expression of HSP72.
Botzler
C
C
GSF-Forschungszentrum fur Umwelt und Gesundheit GmbH, Institut fur Klinische Hamatologie, Munich, Germany.
Kolb
H J
HJ
Issels
R D
RD
Multhoff
G
G
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002451:Cell Compartmentation; D002470:Cell Survival; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D004915:Leukemia, Erythroblastic, Acute / Q000276:immunology*; D010742:Phospholipid Ethers / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018840:HSP70 Heat-Shock Proteins; D010742:Phospholipid Ethers; C026659:edelfosine