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Brian B. Burkey, MD; Geneva M. Omann, PhD; Gregory T. Wolf, MD

Arch Otolaryngol Head Neck Surg. 1991;117(11):1281-1286.

Abstract
• Interleukin 2–activated peripheral blood lymphocytes (lymphokine-activated killer [LAK] cells) have been shown to lyse tumor cells in a nonspecific fashion. Although the mechanisms involved in this cell-mediated lysis are unknown, previous work has shown that T-lymphocyte—mediated cytolysis is associated with massive fluctuations in the intracellular calcium concentration within target cells. Studies were undertaken to determine whether intracellular calcium concentration changes were associated with LAK-mediated cytotoxicity and to determine the effects of calcium channel blockade on in vitro cell-mediated cytotoxicity. Natural killer (NK) and LAK cell cytotoxicity in vitro were measured against head and neck squamous cell carcinoma (UMSCC-11a and UMSCC-38) and Daudi cell lines. Assays were performed in parallel with flow cytometry to measure changes in intracellular calcium concentration within the target cells. Compared with NK cells, LAK cells showed enhanced cytotoxicity against the UMSCC-11a and Daudi lines but not the UMSCC-38 cell line. Both NK and LAK cell cytotoxicity against all the target cell lines directly paralleled significant increases in calcium concentration in the target cells. The addition of verapamil hydrochloride inhibited the rise in intracellular calcium concentration in the sensitive target cells and significantly inhibited both NK and LAK cell cytotoxicity in all the cell lines. The NK cell activity was more sensitive than LAK cell activity to verapamil inhibition. These data suggest that changes in the target cell calcium concentration are early and important events in both NK and LAK cell cytotoxicity in vitro.

(Arch Otolaryngol Head Neck Surg. 1991;117:1281-1286)

Author Affiliations
From the Departments of Otolaryngology—Head and Neck Surgery (Drs Burkey and Wolf) and General Surgery and Biological Chemistry (Dr Omann), The University of Michigan Medical Center and The Veterans Affairs Medical Center, Ann Arbor, Mich. Dr Burkey is now with the Department of Otolaryngology, Vanderbilt University Medical Center, Nashville, Tenn.

Footnotes
Accepted for publication July 23, 1991.

Read before the American Society for Head and Neck Surgery, Waikaloa, Hawaii, May 8, 1991.

Reprint requests to the Department of Otolaryngology, Medical Center North, S-1200, Vanderbilt University Medical Center, Nashville, TN 37232 (Dr Burkey).

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