Multiple roles of complement MASP-1 at the interface of innate immune response and coagulation

- MASP-1 is the most abundant protease of the complement lectin pathway.
- MASP-1 initiates lectin pathway activation by cleaving MASP-2.
- MASP-1 has a relaxed substrate specificity compared to the cognate proteases.
- MASP-1 directly activates endothelial cells by cleaving protease activated receptor 4.
- MASP-1 promotes fibrin formation and influences fibrin structure.

MASP-1 is a versatile serine protease that cleaves a number of substrates in human blood. In recent years it became evident that besides playing a crucial role in complement activation MASP-1 also triggers other cascade systems and even cells to mount a more powerful innate immune response. In this review we summarize the latest discoveries about the diverse functions of this multi-faceted protease. Recent studies revealed that among MBL-associated serine proteases, MASP-1 is the one responsible for triggering the lectin pathway via its ability to rapidly autoactivate then cleave MASP-2, and possibly MASP-3. The crystal structure of MASP-1 explains its more relaxed substrate specificity compared to the related complement enzymes. Due to the relaxed specificity, MASP-1 interacts with the coagulation cascade and the kinin generating system, and it can also activate endothelial cells eliciting pro-inflammatory signaling.