Targeting of mannan-binding lectin-associated serine protease-2 confers protection from myocardial and gastrointestinal ischemia/reperfusion injury

Proc Natl Acad Sci U S A. 2011 May 3;108(18):7523-8. doi: 10.1073/pnas.1101748108. Epub 2011 Apr 18.


Complement research experienced a renaissance with the discovery of a third activation route, the lectin pathway. We developed a unique model of total lectin pathway deficiency, a mouse strain lacking mannan-binding lectin-associated serine protease-2 (MASP-2), and analyzed the role of MASP-2 in two models of postischemic reperfusion injury (IRI). In a model of transient myocardial IRI, MASP-2-deficient mice had significantly smaller infarct volumes than their wild-type littermates. Mice deficient in the downstream complement component C4 were not protected, suggesting the existence of a previously undescribed lectin pathway-dependent C4-bypass. Lectin pathway-mediated activation of C3 in the absence of C4 was demonstrated in vitro and shown to require MASP-2, C2, and MASP-1/3. MASP-2 deficiency also protects mice from gastrointestinal IRI, as do mAb-based inhibitors of MASP-2. The therapeutic effects of MASP-2 inhibition in this experimental model suggest the utility of anti-MASP-2 antibody therapy in reperfusion injury and other lectin pathway-mediated disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Complement C4 / deficiency
  • Female
  • Gastrointestinal Tract / pathology*
  • Mannose-Binding Protein-Associated Serine Proteases / deficiency
  • Mannose-Binding Protein-Associated Serine Proteases / immunology
  • Mannose-Binding Protein-Associated Serine Proteases / metabolism*
  • Mice
  • Mice, Knockout
  • Mice, Mutant Strains
  • Microscopy
  • Myocardium / pathology*
  • Reperfusion Injury / immunology
  • Reperfusion Injury / prevention & control*


  • Antibodies, Monoclonal
  • Complement C4
  • MASP-2 protein, mouse
  • Mannose-Binding Protein-Associated Serine Proteases