The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     
 


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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 Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lombardo, E.
Right arrow Articles by Knaus, U. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lombardo, E.
Right arrow Articles by Knaus, U. G.
The Journal of Immunology, 2007, 178: 3731-3739.
Copyright © 2007 by The American Association of Immunologists, Inc.

TLR4-Mediated Survival of Macrophages Is MyD88 Dependent and Requires TNF-{alpha} Autocrine Signalling1

Eleuterio Lombardo2,*,{dagger}, Alberto Alvarez-Barrientos{dagger}, Beatriz Maroto*, Lisardo Boscá{dagger} and Ulla G. Knaus2,*

* Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037; and {dagger} Fundación Centro Nacional de Investigaciones Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain

Modulation of macrophage survival is a critical factor in the resolution of inflammatory responses. Exposure to LPS protects innate immune cells against apoptosis, although the precise pathways responsible for prolongation of macrophage survival remain to be fully established. The goal of this study was to characterize the mechanism of TLR4-mediated survival of murine bone marrow-derived macrophages upon M-CSF withdrawal in more detail. Using a combination of knockout mice and pharmacological inhibitors allowed us to show that TLR4 and TLR2 stimulation promotes long-term survival of macrophages in a MyD88-, PI3K-, ERK-, and NF-{kappa}B-dependent manner. LPS-induced long-term, but not short-term, survival requires autocrine signaling via TNF-{alpha} and is facilitated by a general cytoprotective program, similar to that mediated by M-CSF. TLR4-mediated macrophage survival is accompanied by a remarkable up-regulation of specific cell surface markers, suggesting that LPS stimulation leads to the differentiation of macrophages toward a mixed macrophage/dendritic cell-like phenotype.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by a Ramón y Cajal contract from the Ministerio de Educación y Ciencia of Spain (to E.L.), grants from Mutua Madrileña and Ministerio de Educación y Ciencia SAF2005-03022 (to L.B.), and National Institutes of Health Grant GM037696 (to U.G.K.).

2 Address correspondence and reprint requests to Dr. Eleuterio Lombardo, Fundación Centro Nacional de Investigaciones Cardiovasculares, Calle Melchor Fdez Almagro 3, Madrid, 28029, Spain; E-mail address: elombardo{at}cnic.es or Dr. Ulla G. Knaus, Department of Immunology IMM28, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; E-mail address: uknaus{at}scripps.edu

3 Abbreviations used in this paper: TRIF, Toll/IL-1R domain-containing adaptor-inducing IFN-beta; BMDM, bone marrow-derived macrophage; cIAP, cellular inhibitor of apoptosis protein; iNOS, inducible nitric oxidase; KO, knockout; L929 CM, L929 cell-conditioned medium; LTA, lipoteichoic acid; MDDC, macrophage-derived dendritic cell; MnSOD, manganese superoxide dismutase; ox-LDL, oxidized low-density lipoprotein; PARP, poly(ADP-ribose) polymerase; PCNA, proliferating cell nuclear Ag; PI, propidium iodide; SN, supernatant; WT, wild type; XIAP, X-linked inhibitor of apoptosis protein.




This article has been cited by other articles:


Home page
J. Biol. Chem.Home page
J. Liu, S. Wang, P. Zhang, N. Said-Al-Naief, S. M. Michalek, and X. Feng
Molecular Mechanism of the Bifunctional Role of Lipopolysaccharide in Osteoclastogenesis
J. Biol. Chem., May 1, 2009; 284(18): 12512 - 12523.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
M. Manukyan, P. Nalbant, S. Luxen, K. M. Hahn, and U. G. Knaus
RhoA GTPase Activation by TLR2 and TLR3 Ligands: Connecting via Src to NF-{kappa}B
J. Immunol., March 15, 2009; 182(6): 3522 - 3529.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
J.-H. Kim, S.-J. Kim, I.-S. Lee, M.-S. Lee, S. Uematsu, S. Akira, and K. I. Oh
Bacterial Endotoxin Induces the Release of High Mobility Group Box 1 via the IFN-{beta} Signaling Pathway
J. Immunol., February 15, 2009; 182(4): 2458 - 2466.
[Abstract] [Full Text] [PDF]


Home page
J. Leukoc. Biol.Home page
M. Sundquist and M. J. Wick
Salmonella induces death of CD8{alpha}+ dendritic cells but not CD11cintCD11b+ inflammatory cells in vivo via MyD88 and TNFR1
J. Leukoc. Biol., February 1, 2009; 85(2): 225 - 234.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
W. Chao
Toll-like receptor signaling: a critical modulator of cell survival and ischemic injury in the heart
Am J Physiol Heart Circ Physiol, January 1, 2009; 296(1): H1 - H12.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
S. A. Rushworth and D. J. MacEwan
HO-1 underlies resistance of AML cells to TNF-induced apoptosis
Blood, April 1, 2008; 111(7): 3793 - 3801.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2007 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2007 by The American Association of Immunologists, Inc. All rights reserved.