Journal of Leukocyte Biology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published online as doi:10.1189/jlb.1007701 on March 13, 2008

Published online before print March 13, 2008
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jlb.1007701v1
83/6/1440    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Choi, K.-S.
Right arrow Articles by Yim, C.-Y.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Choi, K.-S.
Right arrow Articles by Yim, C.-Y.
(Journal of Leukocyte Biology. 2008;83:1440-1450.)
© 2008 by Society for Leukocyte Biology

Cytokines secreted by IL-2-activated lymphocytes induce endogenous nitric oxide synthesis and apoptosis in macrophages

Kyoung-Seong Choi*, Eun-Kee Song{dagger} and Chang-Yeol Yim{dagger},1

* Department of Animal Science, Kyungpook National University, Sangju, Republic of Korea; and
{dagger} Department of Internal Medicine, Chonbuk National University Medical School, Research Institute of Clinical Medicine, and Advanced Research Cancer Center, Chonbuk National University Hospital, Chonju, Chonbuk, Republic of Korea

1Correspondence: Department of Internal Medicine, Chonbuk National University Medical School, San 2-20 Geumam-dong, Chonju, Chonbuk 561-712, Republic of Korea. E-mail: cyyim{at}chonbuk.ac.kr

IL-2-activated killer (LAK) cells secrete inflammatory cytokines such as IFN-{gamma} and TNF-{alpha}, 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-{gamma} and TNF-{alpha}, 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 NG-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.

Key Words: programmed cell death • iNOS • carboxy-PTIO • SNAP • p53 • caspase-3






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2008 by the Society for Leukocyte Biology.