The Journal of Immunology, Vol 151, Issue 7 3420-3429, Copyright © 1993 by American Association of Immunologists

ARTICLES

Stimulation of IL-2-activated natural killer cells through the Kp43 surface antigen up-regulates TNF-alpha production involving the LFA-1 integrin

J Aramburu, MA Balboa, A Rodriguez, I Melero, M Alonso, JL Alonso and M Lopez- Botet
Seccion de Inmunologia, Hospital de la Princesa, Madrid, Spain.

We have previously described that a mAb directed against a surface dimer (Kp43) expressed by NK cells was able to regulate cell proliferation, enhance the cytotoxicity of IL-2-activated NK cells, and activate phospholipase D. In this work we have analyzed the ability of the anti-Kp43 mAb to regulate the production of TNF-alpha. Our results show that the stimulation of IL-2-activated NK cells with soluble anti- Kp43 mAb or its F(ab')2 activated the secretion of the cytokine, inasmuch as this effect is associated with the induction of cellular aggregation. The intensity of the Kp43-mediated stimulation varied among different IL-2-activated NK cell samples. Even in those instances where the anti-Kp43 mAb alone could not detectably enhance TNF-alpha production, it displayed a synergistic effect combined to a soluble anti-CD16 mAb, which on its own did not efficiently activate cytokine production. The anti-Kp43 mAb also cooperated with a phorbol ester, although it did not modify the TNF-alpha production triggered by a Ca2+ ionophore. The anti-Kp43-mediated effect, which required the preactivation of cells with IL-2, was inhibited by cycloheximide and actinomycin D and was associated with an increase in the levels of TNF- alpha-specific mRNA. It is noteworthy that the Kp43-mediated production of TNF-alpha was partially inhibited by anti-CD18, anti-CD11a and anti- ICAM-1 mAb that blocked LFA-1-dependent cellular interactions, which impaired NK cell aggregation and, moreover, was dependent on the presence of extracellular Mg2+, thus suggesting that the leukocyte integrin is involved in the activation process triggered through Kp43.

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