Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on July 1, 2008

Published online before print April 24, 2008
This Article
Right arrow Full Text (Reprint (PDF))
Right arrow All Versions of this Article:
jlb.0907652v1
84/1/215    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
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Popovic, M.
Right arrow Articles by Simmet, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Popovic, M.
Right arrow Articles by Simmet, T.
© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0907652

Received for publication September 24, 2007.
Revised March 20, 2008.
Accepted for publication March 26, 2008.

Article

Thrombin-induced expression of endothelial CX3CL1 potentiates monocyte CCL2 production and transendothelial migration

Milan Popovic , Yves Laumonnier , Ladislav Burysek , Tatiana Syrovets , and Thomas Simmet @

Institute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University, Ulm, Germany

@ To whom correspondence should be addressed. E-mail: thomas.simmet{at}uni-ulm.de.


  Abstract

CX3CL1 (fractalkine, neurotactin) is the sole CX3C chemokine. It induces monocyte locomotion in its cleaved form, but in its membrane-anchored form, it also acts as an adhesion molecule. The expression of CX3CL1 is up-regulated in endothelial cells by proinflammatory cytokines such as IL-1 or TNF-{alpha}. Here, we studied the effect of the serine protease thrombin on endothelial CX3CL1 induction and its putative relevance for monocyte function. In HUVEC, thrombin triggered a time- and concentration-dependent expression of CX3CL1 at the mRNA and the protein level as shown by RT-PCR, Western immunoblotting, and flow cytometric analysis. Thrombin induced CX3CL1 by activating protease-activated receptor 1 (PAR1) as demonstrated by the use of PAR1-activating peptide and the PAR1-specific antagonist SCH 79797. The thrombin-induced CX3CL1 expression was NF-{kappa}B-dependent, as shown by EMSA, ELISA, and by inhibition of the NF-{kappa}B signaling pathway by the I{kappa}B kinase inhibitor acety-11-keto-{beta}-boswellic acid or by transient overexpression of a transdominant-negative form of I{kappa}B{alpha}. Upon cocultivation of human monocytes with HUVEC, the thrombin-dependent induction of membrane-anchored CX3CL1 in HUVEC triggered monocyte adhesion and an enhanced release of the MCP-1/CCL2 by monocytes and potentiated the monocyte transendothelial migration. Accordingly, the recombinant extracellular domain of CX3CL1 induced CCL2 release by monocytes. Thus, the thrombin-induced monocyte/endothelial cell cross-talk mediated by increased CX3CL1 expression potentiates the CCL2 chemokine generation that might contribute to the recruitment of monocytes into inflamed areas.

Key Words: Mono-Mac-6 • HUVEC • chemokine • protease-activated receptor 1 • coculture






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