Enhanced susceptibility of cis-diamminedichloroplatinum-treated K562 cells to lysis by peripheral blood lymphocytes and lymphokine activated killer cells.
BACKGROUND
Previous studies have reported that cis-diamminedichloroplatinum (II) (CDDP) exhibits various immunomodulating activities. The current study investigates the effect of CDDP on the susceptibility of K562 cells to lysis by peripheral blood lymphocytes (PBL), natural killer (NK) cells, and lymphokine activated killer (LAK) cells.


METHODS
Cytotoxicity was determined by the 51Cr release assay.


RESULTS
Treatment of K562 cells with CDDP at 10 micrograms/ml or more for 3 hours or more enhanced their susceptibility to lysis by PBL. This CDDP-mediated enhancement of lysis was observed by PBL derived from healthy donors and from patients with urinary bladder tumor or with other malignant and nonmalignant urologic diseases. The CDDP-induced enhancement of K562 cell susceptibility to lysis by PBL also was observed when purified NK cells and LAK cells were used as effector cells. The CDDP analog, carboplatin, enhanced the susceptibility of K562 cells to lysis by PBL, but treatment with transdiamminedichloroplatinum (II) had no effect. Several experiments were done to investigate the mechanism of the enhanced susceptibility of CDDP-treated K562 cells to lysis by PBL. Treatment of K562 cells with CDDP had no effect on the expression of major histocompatibility complex (MHC) Class I, MHC Class II, neural cellular adhesion molecule, and leukocyte function antigen-1 on the tumor cells. The frequency of target cell conjugates to PBL was not changed by CDDP-treated K562 cells. Pretreatment of K562 cells with CDDP and lysosomotrophic agents (L-leucine-methyl-ester or chloroquine) abrogated their enhanced susceptibility to lysis by PBL. CDDP treatment of K562 cells did not augment their sensitivity to alpha-interferon, gamma-interferon, tumor necrosis factor alpha, or natural killer cytotoxic factor (NKCF). Treatment of effector cells with CDDP had no effect on their cytotoxic function.


CONCLUSIONS
These results demonstrate that CDDP has a direct effect on the K562 target cells, rendering them more susceptible to lysis by PBL, NK cells, and LAK cells. In addition, the result suggest that CDDP-mediated enhancement of target cell lysis is not attributable to changes of surface membrane antigen expression or recruitment of precursor cells but to processing of CDDP by the cells. The possible mechanisms of the effect of CDDP on K562 cells and clinical implications are discussed.
Mizutani
Y
Y
Department of Urology, Faculty of Medicine, Kyoto University, Japan.
Bonavida
B
B
Nio
Y
Y
Yoshida
O
O
D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000187:drug effects; D000954:Antigens, Surface / Q000187:drug effects; D016190:Carboplatin / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004151:Dipeptides / Q000494:pharmacology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology*; D007694:Killer Cells, Natural / Q000502:physiology*; D055646:Killer Factors, Yeast; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology* / Q000503:physiopathology*; D008222:Lymphokines / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000494:pharmacology; D013237:Stereoisomerism; D013601:T-Lymphocytes / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D004151:Dipeptides; D007166:Immunosuppressive Agents; D055646:Killer Factors, Yeast; D008222:Lymphokines; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; C045139:leucyl-leucine-methyl ester; C034697:transplatin; D002738:Chloroquine; D007372:Interferons; D016190:Carboplatin; D002945:Cisplatin