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Department of Parasitology, Yamagata University School of Medicine, Yamagata 990-23, Japan [A. A., T. I., F. S.], and Nacogdoches, Texas 75963-1548 [E. J. C.]
Rat neutrophils stimulated with phorbol 12-myristate 13-acetate, Bacillus Calmette-Guerin, zymosan A, and ß-1,3-D-glucan from Alcaligenes faecalis showed cytotoxicity to various tumor cells. Hydrogen peroxide was shown to be an effector molecule in tumor cytotoxicity by inhibition using various active oxygen scavengers. The following findings suggest that tumor cytotoxicity by rat neutrophils stimulated with the four reagents mentioned above is regulated by Na+/H+ exchange: (a) an increase in extracellular pH (pHo) from 6.5 to 8.0 resulted in enhancement of both tumor cytotoxicity and H2O2 production; (b) amiloride and its derivatives, inhibitors of Na+/H+ exchange, inhibited both functions of neutrophils mentioned above; (c) amiloride reduced intracellular pH (pHi) of neutrophils stimulated with the four reagents; (d) a decrease in the extracellular concentration of Na+ ([Na+]o) inhibited H2O2 production; (e) monensin, a Na+/H+ exchange ionophore, enhanced tumor cytotoxicity by neutrophils.
1 To whom requests for reprints should be addressed.
Received 3/ 7/91. Accepted 4/ 9/91.
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A. Lardner The effects of extracellular pH on immune function J. Leukoc. Biol., April 1, 2001; 69(4): 522 - 530. [Abstract] [Full Text] |
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