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Thromb Haemost 2006; 95(01): 151-158
DOI: 10.1160/TH05-07-0465
Cellular Proteolysis and Oncology
Schattauer GmbH

EMMPRIN (CD 147) is a central activator of extracellular matrix degradation by Chlamydia pneumoniae-infected monocytes.

Implications for plaque rupture
Roland Schmidt
1   Deutsches Herzzentrum und 1. Medizinische Klinik
,
Vanessa Redecke
1   Deutsches Herzzentrum und 1. Medizinische Klinik
,
Yoshi Breitfeld
1   Deutsches Herzzentrum und 1. Medizinische Klinik
,
Nina Wantia
2   Institut für Mikrobiologie, Immunologie und Hygiene, Klinikum rechts der Isar, Technische Universität München
,
Thomas Miethke
2   Institut für Mikrobiologie, Immunologie und Hygiene, Klinikum rechts der Isar, Technische Universität München
,
Steffen Massberg
1   Deutsches Herzzentrum und 1. Medizinische Klinik
,
Sina Fischel
1   Deutsches Herzzentrum und 1. Medizinische Klinik
,
Franz-Josef Neumann   *
1   Deutsches Herzzentrum und 1. Medizinische Klinik
,
Albert Schömig
1   Deutsches Herzzentrum und 1. Medizinische Klinik
,
Andreas E. May
3   Medizinische Klinik III, Klinikum der Eberhard-Karls-Universität Tübingen, Tübingen, Germany
› Author AffiliationsFinancial support: This work was supported by a grant to A. E. M. from the Wilhelm-Sander-Stiftung (2000. 113. 1).
Further Information

Publication History

Received 03 July 2005

Accepted after resubmission 11 November 2005

Publication Date:
28 November 2017 (online)

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Summary

Chlamydia (C.) pneumoniae are thought to infect monocytes and use them as vectors into the vessel wall, where they may accelerate atherosclerosis. We investigated the effects of C. pneumoniae on monocytic matrix metalloproteinase (MMP) activation with focus on the role of the extracellular matrix metalloproteinase inducer EMMPRIN. Human monocytes or monocytic MonoMac6 cells were infected with C. pneumoniae. Infection enhanced mRNA-and surface expression of EMMPRIN and Membrane-type-1 Matrix Metalloproteinase (MT1-MMP), plus the secretion of MMP-7, MMP-9 and the urokinase receptor (uPAR). Chlamydial heat shock protein 60 was identified to be partially responsible for EMMPRIN and MMP-9 induction, while C. trachomatis-infection had no stimulatory effect, indicatinga C. pneumoniae-specific activation pathway. Suppression of EMMPRIN by gene silencing almost completely hindered the induction of MT1-MMP and MMP-9 by C. pneumoniae, suggesting a predominant regulatory role for EMMPRIN. Moreover, C. pneumoniae-infected monocytes exhibited increased MMP-and plasmin-dependent migration through “matrigel”. Additionally, incubation of SMCs with supernatants of C. pneumoniae-infected monocytes induced MMP-2 activation, which was inhibited by IL1-Receptor antagonist or anti-IL-6-mAb, indicating paracrine intercellular activation pathways. In conclusion,C. pneumoniae induce MMP activity directly in monocytes through an EMMPRINdependent pathway and indirectly in SMCs via monocytederived cytokines.

Keywords

EMMPRIN; MMPs - C. pneumoniae; monocytes - plaque rupture

* Current address of FJN: Herzzentrum Bad Krozingen, Südring 15, D-79189 Bad Krozingen, Germany


 

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