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Cooperation between MASP-1 and MASP-2 in the generation of C3 convertase through the MBL pathway

Mette Møller-Kristensen1, Steffen Thiel, Anders Sjöholm

  • 1Department of Medical Microbiology and Immunology, University of Aarhus, Denmark.

International Immunology
|December 22, 2006
PubMed

Insights

Mannan-binding lectin (MBL) activates complement factor C3 via MBL-associated serine proteases (MASP)-1 and MASP-2. This study reveals MASP-1

Area of Science:

  • Immunology
  • Innate Immunity
  • Complement System

Background:

  • The complement system is crucial for innate immunity, with three pathways converging on C3 cleavage.
  • Mannan-binding lectin (MBL) plays a role in initiating complement activation.
  • The precise roles of MBL-associated serine proteases (MASPs), particularly MASP-1, require further elucidation.

Purpose of the Study:

  • To investigate the mechanism of C3 activation on a mannan-coated surface mediated by MBL.
  • To determine the specific roles of MASP-1 and MASP-2 in MBL-driven complement activation.
  • To clarify the involvement of the alternative pathway in this process.

Main Methods:

  • Investigated C3b deposition on mannan-coated surfaces using human serum at high concentration (17%).
  • Utilized serum depleted of specific complement factors and MASPs for functional reconstitution experiments.
  • Assessed the impact of MASP-1, MASP-2, and MASP-3 on C3 activation.

Main Results:

  • MBL promoted C3 activation via MASP-1 and MASP-2 at high serum concentrations, with minimal alternative pathway involvement.
  • Reconstitution of MASP-deficient serum with MASP-1 and MASP-2 showed a synergistic effect, inhibited by MASP-3.
  • C3b deposition was dependent on C2 and C4 but not factor B, confirming the lectin pathway's role.

Conclusions:

  • MASP-1 collaborates with MASP-2 in generating the C3 convertase, a key step in complement activation.
  • This collaborative function of MASP-1 and MASP-2 is observable at high serum concentrations.
  • The study elucidates a specific function for the previously considered 'orphan protease' MASP-1.

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