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Complement protease MASP-1 activates human endothelial cells: PAR4 activation is a link between complement and

Márton Megyeri1, Veronika Makó, László Beinrohr

  • 1Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest, Hungary.

Journal of Immunology (Baltimore, Md. : 1950)
|August 12, 2009
PubMed

Insights

Mannose-binding lectin-associated serine protease-1 (MASP-1) activates endothelial cells by targeting protease-activated receptor 4 (PAR4). This finding reveals a novel link between complement activation and inflammation, impacting endothelial cell function.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • The complement system plays a role in inflammatory responses.
  • Mannose-binding lectin-associated serine protease-1 (MASP-1) is a key protease in the complement lectin pathway, but its function is not fully understood.

Purpose of the Study:

  • To investigate the physiological function of MASP-1 in endothelial cells.
  • To determine if MASP-1 can modulate endothelial cell signaling pathways and identify its potential targets.

Main Methods:

  • Utilized cultured human umbilical vein endothelial cells (HUVECs).
  • Assessed activation of Ca(2+) signaling, NF-kappaB, and p38 MAPK pathways.
  • Investigated the role of MASP-1's proteolytic activity and identified protease-activated receptor 4 (PAR4) as a target.
  • Quantified PAR4 mRNA and measured membrane-bound intact PAR4 levels post-MASP-1 treatment.

Main Results:

  • MASP-1, but not MASP-2, activated Ca(2+) signaling, NF-kappaB, and p38 MAPK pathways in HUVECs.
  • MASP-1's proteolytic activity was essential for this activation, indicating a protease-activated receptor (PAR) mechanism.
  • PAR4 was identified as a direct target of MASP-1.
  • Functional PAR4 and its mRNA were present in HUVECs, and MASP-1 treatment reduced membrane-bound intact PAR4.

Conclusions:

  • MASP-1 activates endothelial cells through PAR4, linking complement activation to endothelial cell function.
  • MASP-1-induced PAR4 activation may contribute to the development of inflammatory reactions.
  • This study elucidates a novel mechanism in complement-mediated inflammation.

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