표적세포의 Nitric oxide 합성이 LAK 세포의 세포독성에 대한 예민도에 미치는 영향

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

  • 박성일 (전북대학교 의과대학 내과학교실) ;
  • 박주형 (전북대학교 의과대학 내과학교실) ;
  • 이치국 (전북대학교 의과대학 내과학교실) ;
  • 김신재 (전북대학교 의과대학 내과학교실) ;
  • 최보금 (전북대학교 의과대학 내과학교실) ;
  • 곽재용 (전북대학교 의과대학 내과학교실) ;
  • 임창열 (전북대학교 의과대학 내과학교실)
  • Park, Sung Il (Department of Internal Medicine, Chonbuk National University Medical School) ;
  • Park, Ju Hyung (Department of Internal Medicine, Chonbuk National University Medical School) ;
  • Lee, Chi Kug (Department of Internal Medicine, Chonbuk National University Medical School) ;
  • Kim, Shin Chae (Department of Internal Medicine, Chonbuk National University Medical School) ;
  • Choi, Bo Geum (Department of Internal Medicine, Chonbuk National University Medical School) ;
  • Kwak, Jae Yong (Department of Internal Medicine, Chonbuk National University Medical School) ;
  • Yim, Chang Yeol (Department of Internal Medicine, Chonbuk National University Medical School)
  • 발행 : 2001.08.31

초록

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.

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