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

Roland Schmidt; Vanessa Redecke; Yoshi Breitfeld; Nina Wantia; Thomas Miethke; Steffen Massberg; Sina Fischel; Franz-Josef Neumann; Albert Schömig; Andreas E. May

doi:10.1160/TH05-07-0465

Thrombosis and Haemostasis, Table of Contents

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

¹Deutsches Herzzentrum und 1. Medizinische Klinik

,

Vanessa Redecke

¹Deutsches Herzzentrum und 1. Medizinische Klinik

,

Yoshi Breitfeld

¹Deutsches Herzzentrum und 1. Medizinische Klinik

,

Nina Wantia

²Institut für Mikrobiologie, Immunologie und Hygiene, Klinikum rechts der Isar, Technische Universität München

,

Thomas Miethke

²Institut für Mikrobiologie, Immunologie und Hygiene, Klinikum rechts der Isar, Technische Universität München

,

Steffen Massberg

¹Deutsches Herzzentrum und 1. Medizinische Klinik

,

Sina Fischel

¹Deutsches Herzzentrum und 1. Medizinische Klinik

,

Franz-Josef Neumann^*

¹Deutsches Herzzentrum und 1. Medizinische Klinik

,

Albert Schömig

¹Deutsches Herzzentrum und 1. Medizinische Klinik

,

Andreas E. May

³Medizinische Klinik III, Klinikum der Eberhard-Karls-Universität Tübingen, Tübingen, Germany

› Author Affiliations

Abstract

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

Full Text

References

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