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Target cell-induced apoptosis of interleukin-2-activated human natural
killer cells: roles of cell surface molecules and intracellular events
A Yamauchi, K Taga, HS Mostowski and ET Bloom
Division of Cellular and Gene Therapies, Center for Biologics Evaluation
Research, Food and Drug Administration.
We previously reported that natural killer (NK)-sensitive target cells,
K562, kill interleukin-2-stimulated (lymphokine-activated killer [LAK]) but
not unstimulated NK cells. We have now investigated the molecular basis of
this phenomenon. Soluble monoclonal antibody (MoAb) to CD18 inhibited 75%
of K562-induced DNA fragmentation and membrane disruption, whereas blocking
MoAb to Fas partially inhibited only the DNA fragmentation. MoAbs to CD2,
CD11a, CD11b, B7, or CD16 had limited or no effect on K562-induced death of
LAK cells. Receptor ligation with either immobilized MoAb to CD18 or Fas
induced membrane disruption and DNA degradation in LAK cells independently
of K562, and MoAb to CD18, CD11a, or CD11b enhanced DNA fragmentation
induced by anti-Fas. Fas-L- transfected Raji cells also killed LAK cells,
but only if Fas-L expression was amplified. K562 cells rapidly triggered
protein phosphorylation in LAK cells, and the tyrosine kinase inhibitor,
Herbimycin A, inhibited DNA fragmentation and membrane disruption. Protease
inhibitors strongly suppressed K562-mediated DNA fragmentation of LAK
cells, but not membrane disruption. In conclusion, (1) K562- induced death
of LAK cells involves primarily CD18, although other molecules, such as
Fas, may also be involved; (2) K562-mediated apoptosis of LAK cells
requires tyrosine phosphorylation and protease activity; (3) engagement of
Fas by immobilized MoAb or Fas-L on target cells can also kill LAK cells;
and (4) Fas-immobilized MoAb synergizes with coimmobilized MoAb to CD11a,
CD11b, or CD18 for LAK cell killing. Activation-induced death of NK cells
may represent a mechanism for NK cell regulation.
Volume 87,
Issue 12,
pp. 5127-5135,
06/15/1996
Copyright © 1996 by The American Society of Hematology
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