NK cell-induced cytotoxicity is dependent on a Ca2+ increase in the target.
In previous work we showed that programmed cell death (PCD) in thymocytes is mediated by a sustained increase in cytosolic Ca2+ concentration, resulting in the activation of an endogenous endonuclease, DNA fragmentation, and cell death. In this study we investigated the roles of Ca2+ and DNA fragmentation in target cell killing by natural killer (NK) cells. The effector cells induced a rapid, sustained increase in cytosolic Ca2+ concentration in Jurkat target cells. Buffering the target cell cytosolic Ca2+ with the Ca2(+)-selective dye, quin-2, prevented target cell killing. Extensive DNA fragmentation was associated with killing in every target tested, and this response was also blocked by quin-2. The endonuclease inhibitor, aurintricarboxylic acid, inhibited both DNA fragmentation and killing without influencing the Ca2+ increase in target cells. Thus, it is concluded that NK cell killing depends on a Ca2+ increase and appears to involve endogenous endonuclease activation in target cells.
McConkey
D J
DJ
Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
Chow
S C
SC
Orrenius
S
S
Jondal
M
M
D000634:Aminoquinolines / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001312:Aurintricarboxylic Acid / Q000008:administration & dosage / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival; D002859:Chromium Isotopes; D003600:Cytosol / Q000276:immunology / Q000473:pathology; D003602:Cytotoxicity, Immunologic / Q000235:genetics*; D004247:DNA / Q000276:immunology*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D014407:Tumor Cells, Cultured
D000634:Aminoquinolines; D002859:Chromium Isotopes; D005456:Fluorescent Dyes; D001312:Aurintricarboxylic Acid; C035738:Quin2-acetoxymethyl ester; D004247:DNA; D002118:Calcium