HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print March 13, 2008

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.1007701v1 83/6/1440    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Choi, K.-S. Articles by Yim, C.-Y. Search for Related Content PubMed PubMed Citation Articles by Choi, K.-S. Articles by Yim, C.-Y.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1007701

Received for publication October 21, 2007.
Revised February 15, 2008.
Accepted for publication February 18, 2008.

Article

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

Kyoung-Seong Choi ^*, Eun-Kee Song , and Chang-Yeol Yim ^@

*Department of Animal Science, Kyungpook National University, Sangju, Republic of Korea; and 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

^@ To whom correspondence should be addressed. E-mail: cyyim{at}chonbuk.ac.kr.

	Abstract

IL-2-activated killer (LAK) cells secrete inflammatory cytokines such as IFN- and TNF-, 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- and TNF-, 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.

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