The human lymphokine leukoregulin induces cell resistance to complement-mediated lysis.
Leukoregulin (LR) is a lymphokine secreted by human natural killer (NK) cells. Its effect on the susceptibility of K562 human erythroleukemic cells to lysis by antibody and complement was examined. As reported here, treatment of K562 cells with LR for 60 min at 37 degrees C confers on them resistance to complement damage. The LR-induced state of complement resistance is transient and the cells recover within 4-6 h unless a second dose of LR is added. The protective action of LR was observed using both conventional 51Cr-release and trypan blue inclusion assays. The protein synthesis inhibitors puromycin and cycloheximide and the protein kinase inhibitors tamoxifen, polymyxin B and W-7, could each block this action of LR. Fewer membrane attack complexes were found, following complement activation, on LR-treated than control cells. These results suggest that LR increases the capacity of K562 cells to down-regulate complement activation or repair the complement damage, possibly by inducing synthesis of defense proteins and/or activation of protective protein kinases.
Fishelson
Z
Z
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Shlanger
S
S
Bomstein
Y
Y
Evans
C H
CH
D000912:Antibodies, Neoplasm / Q000276:immunology; D002118:Calcium / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D015938:Complement Membrane Attack Complex / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D008222:Lymphokines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000912:Antibodies, Neoplasm; D015938:Complement Membrane Attack Complex; D008222:Lymphokines; D047428:Protein Kinase Inhibitors; D011500:Protein Synthesis Inhibitors; C044162:leukoregulin; D003165:Complement System Proteins; D002118:Calcium