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International Immunology Advance Access originally published online on December 20, 2006
International Immunology 2007 19(2):141-149; doi:10.1093/intimm/dxl131
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

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

Mette Møller-Kristensen1, Steffen Thiel1, Anders Sjöholm2,{dagger}, Misao Matsushita3 and Jens C. Jensenius1

1 Department of Medical Microbiology and Immunology, University of Aarhus, Denmark
2 Institute of Laboratory Medicine, Section of Microbiology, Immunology, and Glycobiology, University of Lund, Sweden
3 Institute of Glycotechnology and Department of Applied Biochemistry, Tokai University, Hiratsuka, Japan

Correspondence to: S. Thiel; E-mail: st{at}microbiology.au.dk

The complement system is an important part of the innate immune system. Three pathways, the classical, the alternative and the lectin pathway, lead to the cleavage of complement factor C3, a central event in the activation of the complement system. We investigated the deposition of C3b (solid-phase C3 activation product) on a mannan-coated surface at high concentration of human serum (17%). At these conditions, mannan-binding lectin (MBL) promoted the activation of C3 through the combined action of MBL-associated serine protease (MASP)-1 and MASP-2 without appreciable involvement of the alternative pathway. In serum depleted of MASP-1, MASP-2 and MASP-3, we observed synergetic effect of reconstitution with MASP-1 and MASP-2. This was inhibited by MASP-3. No C3b deposition was observed with C2- or C4-depleted serum. Depletion of factor B had no effect on the MBL–MASP-promoted C3b deposition. Our results demonstrate a function of the orphan protease MASP-1 by providing evidence that this enzyme collaborates with MASP-2 in the generation of C3 convertase, a process observable at high serum concentration, but not at low serum concentration.

Keywords: C3 activation, complement, lectin pathway, mannan-binding lectin

{dagger} He died of cancer on June 1st 2006. He will be sorely missed both as a beloved friend and most capable colleague.

Transmitting editor: A. Falus


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