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

Thromb Haemost. 2006 Jan;95(1):151-8.

Abstract

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, indicating a 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 EMMPRIN-dependent pathway and indirectly in SMCs via monocyte-derived cytokines.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atherosclerosis / enzymology*
  • Atherosclerosis / microbiology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / pharmacology
  • Basigin / genetics
  • Basigin / metabolism*
  • Cell Line
  • Cell Movement
  • Chaperonin 60 / genetics
  • Chaperonin 60 / pharmacology
  • Chlamydophila pneumoniae / isolation & purification*
  • Collagen
  • Drug Combinations
  • Extracellular Matrix / metabolism
  • Humans
  • Laminin
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • Matrix Metalloproteinases, Membrane-Associated
  • Monocytes / drug effects
  • Monocytes / enzymology*
  • Monocytes / microbiology
  • Muscle, Smooth, Vascular / enzymology
  • Myocytes, Smooth Muscle / enzymology
  • Paracrine Communication
  • Proteoglycans
  • RNA Interference
  • RNA, Messenger / metabolism
  • Recombinant Proteins / pharmacology
  • Rupture, Spontaneous / enzymology
  • Rupture, Spontaneous / microbiology

Substances

  • BSG protein, human
  • Bacterial Proteins
  • Chaperonin 60
  • Drug Combinations
  • Laminin
  • Proteoglycans
  • RNA, Messenger
  • Recombinant Proteins
  • matrigel
  • Basigin
  • Collagen
  • Matrix Metalloproteinases
  • Matrix Metalloproteinases, Membrane-Associated
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9