Immune Netw.  2001 Aug;1(2):162-169. 10.4110/in.2001.1.2.162.

Effect of target cell nitric oxide synthesis on the sensitivity to lymphokine-activated killer cell cytotoxicity

• Park SI
• Park JH
• Lee CK
• Kim SC
• Choi BG
• Kwak JY
• Yim CY

• KMID: 2054227
• DOI: http://doi.org/10.4110/in.2001.1.2.162

Abstract

BACKGROUND: Nitric oxide (NO), a cytotoxic molecule is produced in various tissues including tumor cells during interleukin-2 (IL-2) therapy . Lymphokine-activated killer (LAK) cells are induced during IL-2 therapy, and have cytotoxic activity against tumor cells. The current study investigated the effects of NO synthesized in target cells or exposure of target cells to NO on the sensitivity of target cells to LAK cell cytotoxicity.
METHODS
Cytotoxicity was measured using 4 h chromium release assays. LAK cells which were induced by a 4 day incubation of BALB/c mouse splenocytes with IL-2 (6,000 IU/mL) were employed as effector cells. RD-995 skin tumor cells originated from a C3H/HeN mouse were employed as target cells. NO synthesis in target cells was induced by a 24 h incubation of RD-995 cells with IFN gamma (25 U/mL), TNF (50 U/mL) and IL-1 (20 U/mL). S-nitrosyl acetylpenicillamine (SNAP), an NO donor, was used to expose target cells to NO. N(G) -monomethyl-L-arginine (MLA) and carboxy-PTIO were added during cytotoxicity assays to inhibit NO synthesis, and to scavenge NO produced by target cells, respectively.
RESULTS
Sensitivity of NO-producing RD-995 cells to LAK cell cytotoxicity was decreased by addition of MLA and carboxy-PTIO during cytotoxicity assays. However, the two reagents had no effect on the sensitivity of non-NO-producing RD-995 cells. Pretreatment of RD-995 target cells with SNAP increased the sensitivity in comparison with untreated cells.
CONCLUSIONS
Sensitivity of target cells to LAK cell cytotoxicity is increased by target cell NO synthesis or exposure to NO. Further studies are needed to evaluate whether these in vitro results have relevance to in vivo phenomena.

Keyword

IL-2; lymphocyte; cytotoxicity; nitric oxide; tumor

MeSH Terms

Animals
Chromium
Humans
Indicators and Reagents
Interleukin-1
Interleukin-2
Killer Cells, Lymphokine-Activated*
Lymphocytes
Mice
Nitric Oxide*
Skin
Tissue Donors
Chromium
Indicators and Reagents
Interleukin-1
Interleukin-2
Nitric Oxide