The Journal of Immunology, Vol 144, Issue 3 1042-1045, Copyright © 1990 by American Association of Immunologists

ARTICLES

Protease inhibitors block the macrophage-mediated inhibition of tumor cell mitochondrial respiration

R Kilbourn and G Lopez-Berestein
Immunobiology and Drug Carriers Section, University of Texas M. D. Anderson Cancer Center, Houston 77030.

The antitumor activity of activated macrophages toward tumor cells, in vitro, appears to involve the production of toxic nitrogen intermediates. These intermediates, particularly nitric oxide, have been shown to cause the inhibition of cell division and to decrease cellular respiration by inhibiting electron transport. We studied the effects of proteolytic inhibitors on macrophage-mediated inhibition of L1210 tumor cell respiration and DNA synthesis, and found that chloromethyl ketone derivatives, which covalently modify serine proteases, can block macrophage cytotoxicity. Furthermore, these inhibitors decrease nitrite production by activated macrophages suggesting that the mechanism of action involves the inhibition of nitric oxide production.

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