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Cytokines secreted by IL‐2‐activated lymphocytes induce endogenous nitric oxide synthesis and apoptosis in macrophages
Author(s) -
Choi KyoungSeong,
Song EunKee,
Yim ChangYeol
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1007701
Subject(s) - biology , nitric oxide , endogeny , apoptosis , microbiology and biotechnology , macrophage , immunology , biochemistry , in vitro , endocrinology
IL‐2‐activated killer (LAK) cells secrete inflammatory cytokines such as IFN‐γ and TNF‐α, which can induce NO synthesis (NOS). In this study, we investigated IL‐2‐activated lymphocyte‐mediated macrophage apoptosis via NOS. LAK cells and their culture supernatants induced NOS in murine macrophages. NOS was markedly inhibited by blocking antibodies to IFN‐γ and TNF‐α, suggesting the key role of these lymphocyte cytokines in mediating NOS. Endogenous NO production inhibited macrophage proliferation and induced apoptosis in concordance with p53 accumulation and caspase‐3 activation, processes that were inhibited by N G ‐monomethyl‐ l ‐arginine (a NOS inhibitor) and 2‐(4‐carboxyphenyl)‐4,4,5,5‐tetramethylimidazoline‐1‐oxyl 3‐oxide (a NO scavenger). Our study demonstrated a novel, noncontact‐dependent mechanism of macrophage suppression by IL‐2‐activated lymphocytes: induction of growth inhibition and apoptosis of macrophages as a result of endogenous NOS induced by cytokines secreted from IL‐2‐activated lymphocytes.