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The Role of MASP-1/3 in Complement Activation

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Complement Therapeutics

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 735))

Abstract

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.

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Authors and Affiliations

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

    Hideharu Sekine, Minoru Takahashi, Daisuke Iwaki & Teizo Fujita

  2. Fukushima Prefectural General Hygiene Institute, Fukushima, 960-1295, Japan

    Teizo Fujita

Authors
  1. Hideharu Sekine
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  2. Minoru Takahashi
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  3. Daisuke Iwaki
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  4. Teizo Fujita
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Correspondence to Teizo Fujita .

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Editors and Affiliations

  1. Medicine, University Of Pennsylvania Department Of Pathology Laboratory Of, Philadelphia, Pennsylvania, USA

    John D. Lambris

  2. University of Colorado School of Medicin, Aurora, Colorado, USA

    V. Michael Holers

  3. Department of Pathology & Laboratory Med, University of Pennsylvania School of Med, Philadelphia, Pennsylvania, USA

    Daniel Ricklin

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Sekine, H., Takahashi, M., Iwaki, D., Fujita, T. (2013). The Role of MASP-1/3 in Complement Activation. In: Lambris, J., Holers, V., Ricklin, D. (eds) Complement Therapeutics. Advances in Experimental Medicine and Biology, vol 735. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4118-2_3

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