The role of MASP-1/3 in complement activation.

Hideharu Sekine, Minoru Takahashi, Daisuke Iwaki, Teizo Fujita

Department of Immunology, Fukushima Medical University School of Medicine, 1-Hikariga-oka, Fukushima 960-1295, Japan.

Advances in experimental medicine and biology 2013

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The complement system, which consists of more than 30 plasma and cell surface proteins, is activated by three pathways: the classical, lectin, and alternative pathways, leading to the generation of opsonins and pathogen destruction. In the lectin pathway, mannose-binding lectin (MBL) and ficolins act as pattern recognition molecules for pathogens, resulting in the activation of MBL-associated serine proteases (MASPs: MASP-1, MASP-2, and MASP-3). Among these proteases, MASP-2 is a key enzyme that cleaves C4 and C2 to assemble a C3 convertase (C4b2a). However, the physiological function of MASP-1 and MASP-3 remains unclear. To investigate the roles of MASP-1 and MASP-3, we generated a MASP-1- and MASP-3-deficient (M1/3 KO) mouse model and found that the deficient mice lacked alternative pathway activation because factor D (Df) remained as a proenzyme in the serum. MASP-1 and MASP-3 were able to convert the proenzyme of Df to an active form in vitro. In addition, MASP-1 was able to activate MASP-2 and MASP-3 as C1r activates C1s. Thus, MASP-1 and MASP-3 seem to be involved in activation of both the lectin and alternative pathways.

Citation

Hideharu Sekine, Minoru Takahashi, Daisuke Iwaki, Teizo Fujita. The role of MASP-1/3 in complement activation. Advances in experimental medicine and biology. 2013;735:41-53