Abstract
Mannose-binding lectin (MBL) and ficolin are pattern recognition molecules in the complex with the MBL-associated serine proteases (MASPs). Three kinds of MASPs, termed as MASP-1, MASP-2 and MASP-3 have been identified. When MBL or ficolins binds to carbohydrates on the surface of microbes, conformational modifications of these molecules trigger to activate zymogens of MASPs, followed by consequential complement activation. MASP-2 cleaves C4 and C2 to make a C3 convertase, C4b2a. MASP-1 has an ability to cleave C3 directly, although this activity has not been detected in physiological conditions. Natural target molecules for MASP-3 are still discussible. To elucidate the physiological meanings of MASPs, we generated MASPs-deficient mice. Not only MASP-2-deficient mouse but also MASP-1-/MASP-3-deficient mouse reduced activities for C3 deposition on the surface of mannan and zymosan, suggesting MASP-1/3 also contribute the activation of complement by the lectin pathway. Also, MASP-1/3-deficient mice showed the susceptible to an influenza virus.
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Ambrus, G., Gal, P., Kojima, M., Szilagyi, K., Balczer, J., Antal, J., Graf, L., Laich, A., Moffatt, B. E., Schwaeble, W., et al. (2003). Natural substrates and inhibitors of mannan-binding lectin-associated serine protease-1 and -2: a study on recombinant catalytic fragments. J Immunol 170, 1374-1382.
Anders, E. M., Hartley, C. A., and Jackson, D. C. (1990). Bovine and mouse serum beta inhibitors of influenza A viruses are mannose-binding lectins. Proc Natl Acad Sci U S A 87, 4485-4489.
Chen, C. B., and Wallis, R. (2004). Two mechanisms for mannose-binding protein modulation of the activity of its associated serine proteases. J Biol Chem 279, 26058-26065.
Cortesio, C. L., and Jiang, W. (2006). Mannan-binding lectin-associated serine protease 3 cleaves synthetic peptides and insulin-like growth factor-binding protein 5. Arch Biochem Biophys.
Cseh, S., Vera, L., Matsushita, M., Fujita, T., Arlaud, G. J., and Thielens, N. M. (2002). Characterization of the interaction between L-ficolin/p35 and mannan-binding lectin-associated serine proteases-1 and -2. J Immunol 169, 5735-5743.
Dahl, M. R., Thiel, S., Matsushita, M., Fujita, T., Willis, A. C., Christensen, T., Vorup-Jensen, T., and Jensenius, J. C. (2001). MASP-3 and its association with distinct complexes of the mannan-binding lectin complement activation pathway. Immunity 15, 127-135.
de Vries, B., Walter, S. J., Peutz-Kootstra, C. J., Wolfs, T. G., van Heurn, L. W., and Buurman, W. A. (2004). The mannose-binding lectin-pathway is involved in complement activation in the course of renal ischemia-reperfusion injury. Am J Pathol 165, 1677-1688.
Endo, Y., Nakazawa, N., Liu, Y., Iwaki, D., Takahashi, M., Fujita, T., Nakata, M., and Matsushita, M. (2005). Carbohydrate-binding specificities of mouse ficolin A, a splicing variant of ficolin A and ficolin B and their complex formation with MASP-2 and sMAP. Immunogenetics 57, 837-844.
Endo, Y., Nonaka, M., Saiga, H., Kakinuma, Y., Matsushita, A., Takahashi, M., Matsushita, M., and Fujita, T. (2003). Origin of mannose-binding lectin-associated serine protease (MASP)-1 and MASP-3 involved in the lectin complement pathway traced back to the invertebrate, amphioxus. J Immunol 170, 4701-4707.
Endo, Y., Sato, T., Matsushita, M., and Fujita, T. (1996). Exon structure of the gene encoding the human mannose-binding protein-associated serine protease light chain: comparison with complement C1r and C1s genes. Int Immunol 8, 1355-1358.
Endo, Y., Takahashi, M., Nakao, M., Saiga, H., Sekine, H., Matsushita, M., Nonaka, M., and Fujita, T. (1998). Two lineages of mannose-binding lectin-associated serine protease (MASP) in vertebrates. J Immunol 161, 4924-4930.
Fujita, T. (2002). Evolution of the lectin-complement pathway and its role in innate immunity. Nat Rev Immunol 2, 346-353.
Hart, M. L., Ceonzo, K. A., Shaffer, L. A., Takahashi, K., Rother, R. P., Reenstra, W. R., Buras, J. A., and Stahl, G. L. (2005). Gastrointestinal ischemia-reperfusion injury is lectin complement pathway dependent without involving C1q. J Immunol 174, 6373-6380.
Iwaki, D., Kanno, K., Takahashi, M., Endo, Y., Lynch, N. J., Schwaeble, W. J., Matsushita, M., Okabe, M., and Fujita, T. (2006). Small mannose-binding lectin-associated protein plays a regulatory role in the lectin complement pathway. J Immunol 177, 8626-8632.
Ji, X., Azumi, K., Sasaki, M., and Nonaka, M. (1997). Ancient origin of the complement lectin pathway revealed by molecular cloning of mannan binding protein-associated serine protease from a urochordate, the Japanese ascidian, Halocynthia roretzi. Proc Natl Acad Sci U S A 94, 6340-6345.
Liu, Y., Endo, Y., Iwaki, D., Nakata, M., Matsushita, M., Wada, I., Inoue, K., Munakata, M., and Fujita, T. (2005). Human M-ficolin is a secretory protein that activates the lectin complement pathway. J Immunol 175, 3150-3156.
Lynch, N. J., Khan, S. U., Stover, C. M., Sandrini, S. M., Marston, D., Presanis, J. S., and Schwaeble, W. J. (2005). Composition of the lectin pathway of complement in Gallus gallus: absence of mannan-binding lectin-associated serine protease-1 in birds. J Immunol 174, 4998-5006.
Matsushita, M., Endo, Y., and Fujita, T. (2000a). Cutting edge: complement-activating complex of ficolin and mannose-binding lectin-associated serine protease. J Immunol 164, 2281-2284.
Matsushita, M., and Fujita, T. (1992). Activation of the classical complement pathway by mannose-binding protein in association with a novel C1s-like serine protease. J Exp Med 176, 1497-1502.
Matsushita, M., and Fujita, T. (1995). Cleavage of the third component of complement (C3) by mannose-binding protein-associated serine protease (MASP) with subsequent complement activation. Immunobiology 194, 443-448.
Matsushita, M., Kuraya, M., Hamasaki, N., Tsujimura, M., Shiraki, H., and Fujita, T. (2002). Activation of the lectin complement pathway by H-ficolin (Hakata antigen). J Immunol 168, 3502-3506.
Matsushita, M., Thiel, S., Jensenius, J. C., Terai, I., and Fujita, T. (2000b). Proteolytic activities of two types of mannose-binding lectin-associated serine protease. J Immunol 165, 2637-2642.
Moller-Kristensen, M., Wang, W., Ruseva, M., Thiel, S., Nielsen, S., Takahashi, K., Shi, L., Ezekowitz, A., Jensenius, J. C., and Gadjeva, M. (2005). Mannan-binding lectin recognizes structures on ischaemic reperfused mouse kidneys and is implicated in tissue injury. Scand J Immunol 61, 426-434.
Reading, P. C., Morey, L. S., Crouch, E. C., and Anders, E. M. (1997). Collectin-mediated antiviral host defense of the lung: evidence from influenza virus infection of mice. J Virol 71, 8204-8212.
Rossi, V., Cseh, S., Bally, I., Thielens, N. M., Jensenius, J. C., and Arlaud, G. J. (2001). Substrate specificities of recombinant mannan-binding lectin-associated serine proteases-1 and -2. J Biol Chem 276, 40880-40887.
Sato, T., Endo, Y., Matsushita, M., and Fujita, T. (1994). Molecular characterization of a novel serine protease involved in activation of the complement system by mannose-binding protein. Int Immunol 6, 665-669.
Schwaeble, W., Dahl, M. R., Thiel, S., Stover, C., and Jensenius, J. C. (2002). The mannan-binding lectin-associated serine proteases (MASPs) and MAp19: four components of the lectin pathway activation complex encoded by two genes. Immunobiology 205, 455-466.
Selander, B., Martensson, U., Weintraub, A., Holmstrom, E., Matsushita, M., Thiel, S., Jensenius, J. C., Truedsson, L., and Sjoholm, A. G. (2006). Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2. J Clin Invest 116, 1425-1434.
Sorensen, R., Thiel, S., and Jensenius, J. C. (2005). Mannan-binding-lectin-associated serine proteases, characteristics and disease associations. Springer Semin Immunopathol 27, 299-319.
Stengaard-Pedersen, K., Thiel, S., Gadjeva, M., Moller-Kristensen, M., Sorensen, R., Jensen, L. T., Sjoholm, A. G., Fugger, L., and Jensenius, J. C. (2003). Inherited deficiency of mannan-binding lectin-associated serine protease 2. N Engl J Med 349, 554-560.
Stover, C., Endo, Y., Takahashi, M., Lynch, N. J., Constantinescu, C., Vorup-Jensen, T., Thiel, S., Friedl, H., Hankeln, T., Hall, R., et al. (2001). The human gene for mannan-binding lectin-associated serine protease-2 (MASP-2), the effector component of the lectin route of complement activation, is part of a tightly linked gene cluster on chromosome 1p36.2-3. Genes Immun 2, 119-127.
Stover, C. M., Schwaeble, W. J., Lynch, N. J., Thiel, S., and Speicher, M. R. (1999a). Assignment of the gene encoding mannan-binding lectin-associated serine protease 2 (MASP2) to human chromosome 1p36.3–>p36.2 by in situ hybridization and somatic cell hybrid analysis. Cytogenet Cell Genet 84, 148-149.
Stover, C. M., Thiel, S., Thelen, M., Lynch, N. J., Vorup-Jensen, T., Jensenius, J. C., and Schwaeble, W. J. (1999b). Two constituents of the initiation complex of the mannan-binding lectin activation pathway of complement are encoded by a single structural gene. J Immunol 162, 3481-3490.
Takada, F., Seki, N., Matsuda, Y., Takayama, Y., and Kawakami, M. (1995). Localization of the genes for the 100-kDa complement-activating components of Ra-reactive factor (CRARF and Crarf) to human 3q27-q28 and mouse 16B2-B3. Genomics 25, 757-759.
Takahashi, M., Endo, Y., Fujita, T., and Matsushita, M. (1999). A truncated form of mannose-binding lectin-associated serine protease (MASP)-2 expressed by alternative polyadenylation is a component of the lectin complement pathway. Int Immunol 11, 859-863.
Takayama, Y., Takada, F., Nowatari, M., Kawakami, M., and Matsu-ura, N. (1999). Gene structure of the P100 serine-protease component of the human Ra-reactive factor. Mol Immunol 36, 505-514.
Thiel, S., Vorup-Jensen, T., Stover, C. M., Schwaeble, W., Laursen, S. B., Poulsen, K., Willis, A. C., Eggleton, P., Hansen, S., Holmskov, U., et al. (1997). A second serine protease associated with mannan-binding lectin that activates complement. Nature 386, 506-510.
Thielens, N. M., Cseh, S., Thiel, S., Vorup-Jensen, T., Rossi, V., Jensenius, J. C., and Arlaud, G. J. (2001). Interaction properties of human mannan-binding lectin (MBL)-associated serine proteases-1 and -2, MBL-associated protein 19, and MBL. J Immunol 166, 5068-5077.
Vorup-Jensen, T., Petersen, S. V., Hansen, A. G., Poulsen, K., Schwaeble, W., Sim, R. B., Reid, K. B., Davis, S. J., Thiel, S., and Jensenius, J. C. (2000). Distinct pathways of mannan-binding lectin (MBL)- and C1-complex autoactivation revealed by reconstitution of MBL with recombinant MBL-associated serine protease-2. J Immunol 165, 2093-2100.
Wallis, R., and Dodd, R. B. (2000). Interaction of mannose-binding protein with associated serine proteases: effects of naturally occurring mutations. J Biol Chem 275, 30962-30969.
Walsh, M. C., Bourcier, T., Takahashi, K., Shi, L., Busche, M. N., Rother, R. P., Solomon, S. D., Ezekowitz, R. A., and Stahl, G. L. (2005). Mannose-binding lectin is a regulator of inflammation that accompanies myocardial ischemia and reperfusion injury. J Immunol 175, 541-546.
Zundel, S., Cseh, S., Lacroix, M., Dahl, M. R., Matsushita, M., Andrieu, J. P., Schwaeble, W. J., Jensenius, J. C., Fujita, T., Arlaud, G. J., and Thielens, N. M. (2004). Characterization of recombinant mannan-binding lectin-associated serine protease (MASP)-3 suggests an activation mechanism different from that of MASP-1 and MASP-2. J Immunol 172, 4342-4350.
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Takahashi, M., Mori, S., Shigeta, S., Fujita1, T. (2007). Role of MBL-associated Serine Protease (MASP) On Activation of the Lectin Complement Pathway. In: Lambris, J.D. (eds) Current Topics in Innate Immunity. Advances in Experimental Medicine and Biology, vol 598. Springer, New York, NY. https://doi.org/10.1007/978-0-387-71767-8_8
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DOI: https://doi.org/10.1007/978-0-387-71767-8_8
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