We read with great interest the article by Hayashi et al. (1), in which the authors report the generation of two new mouse strains, specifically deficient in MASP-1 or MASP-3. In their study, the authors demonstrated in mice that MASP-1 is indispensable for lectin pathway activation, and MASP-3 is responsible for proteolytic processing of zymogen FD (pro-FD) to FD, the initiating protease of the alternative pathway.
The authors’ findings in these mouse models are in perfect agreement with our previous results obtained with human whole blood, plasma, and serum samples using specific human MASP-1, MASP-2, and MASP-3 inhibitors developed by directed evolution (2, 3). In our prior studies, we showed that a monospecific MASP-1 inhibitor completely prevented lectin pathway activation (2). Using a specific MASP-3 inhibitor, we also demonstrated that MASP-3 is the exclusive activator of pro-FD in resting human blood (3). A publication by another research group also highlighted the important role of MASP-3 in pro-FD activation (4).
The only apparent difference between the previous human results and the new mouse results is the role of MASP-1 in LPS-driven alternative pathway activation (5). In this respect, the mouse and the human complement systems might be different, but not necessarily at the level of MASP-1 (6–8).
In all, by comparing our and other previous human results with the new mouse results of Hayashi et al. (1), we conclude that the major functions of MASP-1 and MASP-3 have been conserved during mammalian evolution, although minor species-specific differences may exist.