Abstract:
:Several lines of evidence suggest that nitric oxide (NO), generated through nitric oxide synthase (NOS) by cleavage of terminal guanidino nitrogen from L-arginine, mediates tumor cell killing by mononuclear phagocytes. Natural killer (NK) cells are cytotoxic effector cells that lyse a variety of tumor and virus-infected cells in a MHC-unrestricted manner. NK cells cultured with interleukin 2 proliferate and acquire the ability to lyse a wide range of targets, including NK-resistant tumor cells (LAK activity). The present study was designed to investigate whether a NOS pathway exists in fresh or IL-2-activated NK cells and to assess the importance of NO synthesis in their activation and cytotoxic functions. NKR-P1 triggering, which is known to induce NK cell activation and mediate reverse ADCC, was able to induce arginine metabolism with consequent increase of nitrite and citrulline levels. Moreover, stimulated NO synthesis leads to guanylate cyclase activity with consequent cGMP generation. We also report that cytotoxic activities of fresh or IL-2-activated NK cells appear to be dependent on arginine levels in medium. Tumoricidal activity of both these effector cells, assessed against YAC-1 and P815 target cells, respectively, was indeed significantly reduced when cytotoxic assays were performed in arginine-free medium or in the presence of the L-arginine analog L-N-monomethyl-arginine, which inhibits nitroxide formation from L-arginine. Normal levels of cytotoxic activities could be restored by addition of exogenous L-arginine. NO generation by NK and LAK cells, determined as nitrite, citrulline, and cGMP synthesis, correlated well with their cytotoxic activities. Moreover, NOS activity gradually increased during the LAK generation and correlated well with the increasing capability of IL-2-activated NK cells to lyse NK-resistant targets, such as P815.
journal_name
Cell Immunoljournal_title
Cellular immunologyauthors
Cifone MG,Festuccia C,Cironi L,Cavallo G,Chessa MA,Pensa V,Tubaro E,Santoni Adoi
10.1006/cimm.1994.1215subject
Has Abstractpub_date
1994-08-01 00:00:00pages
181-94issue
1eissn
0008-8749issn
1090-2163pii
S0008-8749(84)71215-9journal_volume
157pub_type
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journal_title:Cellular immunology
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journal_title:Cellular immunology
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journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1006/cimm.1993.1144
更新日期:1993-06-01 00:00:00
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journal_title:Cellular immunology
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journal_title:Cellular immunology
pub_type: 杂志文章
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更新日期:1998-05-01 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
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journal_title:Cellular immunology
pub_type: 杂志文章
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更新日期:1993-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:1983-03-01 00:00:00
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journal_title:Cellular immunology
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更新日期:2006-02-01 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1006/cimm.1994.1156
更新日期:1994-06-01 00:00:00
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更新日期:1983-02-01 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
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更新日期:1995-11-01 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
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更新日期:2012-01-01 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
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更新日期:1997-05-01 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1016/0008-8749(85)90180-7
更新日期:1985-01-01 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章,评审
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更新日期:2018-11-01 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
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更新日期:1999-02-01 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
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更新日期:1989-04-15 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1006/cimm.1995.1128
更新日期:1995-07-01 00:00:00
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