Distinct Ca2+ response patterns in human natural killer cells during induction of necrosis or apoptosis of target cells.
Human CD3-, CD16+ natural killer cells (NKs) induced necrosis in the cell line K562 and the minor population of MOLT-4, while induced apoptosis in the majority of MOLT-4, in one-to-one cell interaction. Simultaneous Ca2+ imaging of NK and target cells revealed remarkable differences in changes of cytosolic Ca2+ concentration ([Ca2+]i) during the process of distinct target cell killing. A rapid [Ca2+]i rise in NK was generated within 2 min after contact with any target. For induction of necrosis, the [Ca2+]i rise in NK reached a peak of 580 +/- 195 nM (mean +/- SD, n = 41) and was followed by an abrupt large [Ca2+]i rise in target cells probably due to Ca2+ entry through pores formed by perforin which was released from NK. The interval between onsets of NK and target Ca2+ responses (Tnk-t) was shorter than 3 min in most cases. Target cells were soon permeabilized, and NK Ca2+ responses ceased in 14 +/- 7 min. For induction of apoptosis, NK Ca2+ responses were relatively smaller (405 +/- 125 nM, n = 16), and Tnk-t was widely scattered up to 30 min. NK Ca2+ responses lasted much longer in a form of Ca2+ oscillations (total duration, 66 +/- 33 min) in parallel with target Ca2+ responses, and ceased as apoptotic changes such as cellular and nuclear fragmentation advanced. The difference in Tnk-t suggests that rapid synchronous release of perforin tends to cause necrosis rather than apoptosis. The duration of NK Ca2+ responses suggests that some 'off signals' may be transmitted to NK following recognition of target cell damage.
Honda
Y
Y
Department of Physiology, Tokyo Women's Medical College, Japan.
Miyazaki
S
S
D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000502:physiology*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology* / Q000473:pathology; D009336:Necrosis; D014407:Tumor Cells, Cultured
D002118:Calcium