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EMMPRIN (CD 147) is a central activator of extracellular matrix degradation by Chlamydia pneumoniae-infected monocytes. Implications for plaque rupture
- Source :
- Thrombosis and haemostasis. 95(1)
- Publication Year :
- 2006
-
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.
- Subjects :
- Matrix Metalloproteinases, Membrane-Associated
Myocytes, Smooth Muscle
Matrix metalloproteinase
Biology
medicine.disease_cause
Monocytes
Muscle, Smooth, Vascular
Cell Line
Paracrine signalling
Bacterial Proteins
Cell Movement
Paracrine Communication
medicine
Humans
RNA, Messenger
Metalloproteinase
Matrigel
Rupture, Spontaneous
Monocyte
Hematology
Chaperonin 60
Chlamydophila pneumoniae
Atherosclerosis
Molecular biology
Matrix Metalloproteinases
Recombinant Proteins
Extracellular Matrix
Urokinase receptor
Drug Combinations
medicine.anatomical_structure
Matrix Metalloproteinase 9
Immunology
Basigin
Matrix Metalloproteinase 2
Proteoglycans
RNA Interference
Collagen
Laminin
Extracellular Matrix Degradation
Subjects
Details
- ISSN :
- 03406245
- Volume :
- 95
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Thrombosis and haemostasis
- Accession number :
- edsair.doi.dedup.....019b26019d282c7ba2b398575c6466cf