Advertisement

The Role of MASP-1/3 in Complement Activation

  • Hideharu Sekine
  • Minoru Takahashi
  • Daisuke Iwaki
  • Teizo FujitaEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (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.

Keywords

Alternative Pathway Lectin Pathway Carbohydrate Recognition Domain Alternative Pathway Activation Pattern Recognition Molecule 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Banda NK, Takahashi M, Levitt B, Glogowska M, Nicholas J, Takahashi K, Stahl GL, Fujita T, Arend WP, Holers VM (2010) Essential role of complement mannose-binding lectin-associated serine proteases-1/3 in the murine collagen antibody-induced model of inflammatory arthritis. J Immunol 185:5598–5606CrossRefGoogle Scholar
  2. Barnum SR, Volanakis JE (1985) In vitro biosynthesis of complement protein D by U937 cells. J Immunol 134:1799–1803PubMedGoogle Scholar
  3. Carroll MC (2004) The complement system in regulation of adaptive immunity. Nat Immunol 5:981–986CrossRefGoogle Scholar
  4. Chen CB, Wallis R (2004) Two mechanisms for mannose-binding protein modulation of the activity of its associated serine proteases. J Biol Chem 279:26058–26065CrossRefGoogle Scholar
  5. Cook KS, Groves DL, Min HY, Spiegelman BM (1985) A developmentally regulated mRNA from 3T3 adipocytes encodes a novel serine protease homologue. Proc Natl Acad Sci USA 82:6480–6484CrossRefGoogle Scholar
  6. Cseh S, Vera L, Matsushita M, Fujita T, Arlaud GJ, Thielens NM (2002) Characterization of the interaction between L-ficolin/p35 and mannan-binding lectin-associated serine proteases-1 and -2. J Immunol 169:5735–5743CrossRefGoogle Scholar
  7. Dahl MR, Thiel S, Matsushita M, Fujita T, Willis AC, Christensen T, Vorup-Jensen T, Jensenius JC (2001) MASP-3 and its association with distinct complexes of the mannan-binding lectin complement activation pathway. Immunity 15:127–135CrossRefGoogle Scholar
  8. Degn SE, Hansen AG, Steffensen R, Jacobsen C, Jensenius JC, Thiel S (2009) MAp44, a human protein associated with pattern recognition molecules of the complement system and regulating the lectin pathway of complement activation. J Immunol 183:7371–7378CrossRefGoogle Scholar
  9. Drickamer K (1992) Engineering galactose-binding activity into a C-type mannose-binding protein. Nature 360:183–186CrossRefGoogle Scholar
  10. Drickamer K, Dordal MS, Reynolds L (1986) Mannose-binding proteins isolated from rat liver contain carbohydrate-recognition domains linked to collagenous tails. Complete primary structures and homology with pulmonary surfactant apoprotein. J Biol Chem 261:6878–6887PubMedGoogle Scholar
  11. Endo Y, Sato Y, Matsushita M, Fujita T (1996) Cloning and characterization of the human lectin P35 gene and its related gene. Genomics 36:515–521CrossRefGoogle Scholar
  12. Endo Y, Matsushita M, Fujita T (2011) The role of ficolins in the lectin pathway of innate immunity. Int J Biochem Cell Biol 43:705–712CrossRefGoogle Scholar
  13. Ezekowitz RA, Day LE, Herman GA (1988) A human mannose-binding protein is an acute-phase reactant that shares sequence homology with other vertebrate lectins. J Exp Med 167:1034–1046CrossRefGoogle Scholar
  14. Fujita T (2002) Evolution of the lectin-complement pathway and its role in innate immunity. Nat Rev Immunol 2:346–353CrossRefGoogle Scholar
  15. Garlatti V, Belloy N, Martin L, Lacroix M, Matsushita M, Endo Y, Fujita T, Fontecilla-Camps JC, Arlaud GJ, Thielens NM, Gaboriaud C (2007a) Structural insights into the innate immune recognition specificities of L- and H-ficolins. EMBO J 26:623–633CrossRefGoogle Scholar
  16. Garlatti V, Martin L, Gout E, Reiser JB, Fujita T, Arlaud GJ, Thielens NM, Gaboriaud C (2007b) Structural basis for innate immune sensing by M-ficolin and its control by a pH-dependent conformational switch. J Biol Chem 282:35814–35820CrossRefGoogle Scholar
  17. Hajela K, Kojima M, Ambrus G, Wong KH, Moffatt BE, Ferluga J, Hajela S, Gal P, Sim RB (2002) The biological functions of MBL-associated serine proteases (MASPs). Immunobiology 205:467–475CrossRefGoogle Scholar
  18. Hansen S, Selman L, Palaniyar N, Ziegler K, Brandt J, Kliem A, Jonasson M, Skjoedt MO, Nielsen O, Hartshorn K et al (2010) Collectin 11 (CL-11, CL-K1) is a MASP-1/3-associated plasma collectin with microbial-binding activity. J Immunol 185:6096–6104CrossRefGoogle Scholar
  19. Hoffmann JA, Kafatos FC, Janeway CA, Ezekowitz RA (1999) Phylogenetic perspectives in innate immunity. Science 284:1313–1318CrossRefGoogle Scholar
  20. Holmskov U, Malhotra R, Sim RB, Jensenius JC (1994) Collectins: collagenous C-type lectins of the innate immune defense system. Immunol Today 15:67–74CrossRefGoogle Scholar
  21. Ichijo H, Hellman U, Wernstedt C, Gonez LJ, Claesson-Welsh L, Heldin CH, Miyazono K (1993) Molecular cloning and characterization of ficolin, a multimeric protein with fibrinogen- and collagen-like domains. J Biol Chem 268:14505–14513PubMedGoogle Scholar
  22. Iwaki D, Kanno K, Takahashi M, Endo Y, Lynch NJ, Schwaeble WJ, Matsushita M, Okabe M, Fujita T (2006) Small mannose-binding lectin-associated protein plays a regulatory role in the lectin complement pathway. J Immunol 177:8626–8632CrossRefGoogle Scholar
  23. Iwaki D, Kanno K, Takahashi M, Endo Y, Matsushita M, Fujita T (2011) The role of mannose-binding lectin-associated serine protease-3 in activation of the alternative complement pathway. J Immunol 187:3751–3758CrossRefGoogle Scholar
  24. Jack DL, Klein NJ, Turner MW (2001) Mannose-binding lectin: targeting the microbial world for complement attack and opsonophagocytosis. Immunol Rev 180:86–99CrossRefGoogle Scholar
  25. Krarup A, Gulla KC, Gal P, Hajela K, Sim RB (2008) The action of MBL-associated serine protease 1 (MASP1) on factor XIII and fibrinogen. Biochim Biophys Acta 1784:1294–1300CrossRefGoogle Scholar
  26. La Bonte LR, Pavlov VI, Tan YS, Takahashi K, Takahashi M, Banda NK, Zou C, Fujita T, Stahl GL (2012) Mannose-binding lectin-associated serine protease-1 is a significant contributor to coagulation in a murine model of occlusive thrombosis. J Immunol 188:885–891CrossRefGoogle Scholar
  27. Liu Y, Endo Y, Iwaki D, Nakata M, Matsushita M, Wada I, Inoue K, Munakata M, Fujita T (2005) Human M-ficolin is a secretory protein that activates the lectin complement pathway. J Immunol 175:3150–3156CrossRefGoogle Scholar
  28. Lu J, Tay PN, Kon OL, Reid KB (1996) Human ficolin: cDNA cloning, demonstration of peripheral blood leucocytes as the major site of synthesis and assignment of the gene to chromosome 9. Biochem J 313(Pt 2):473–478CrossRefGoogle Scholar
  29. Matsushita M, 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 176:1497–1502CrossRefGoogle Scholar
  30. Matsushita M, Fujita T (1995) Cleavage of the third component of complement (C3) by mannose-binding protein-associated serine protease (MASP) with subsequent complement activation. Immunobiology 194:443–448CrossRefGoogle Scholar
  31. Matsushita M, Endo Y, Taira S, Sato Y, Fujita T, Ichikawa N, Nakata M, Mizuochi T (1996) A novel human serum lectin with collagen- and fibrinogen-like domains that functions as an opsonin. J Biol Chem 271:2448–2454CrossRefGoogle Scholar
  32. Matsushita M, Endo Y, Fujita T (2000a) Cutting edge: complement-activating complex of ficolin and mannose-binding lectin-associated serine protease. J Immunol 164:2281–2284CrossRefGoogle Scholar
  33. Matsushita M, Thiel S, Jensenius JC, Terai I, Fujita T (2000b) Proteolytic activities of two types of mannose-binding lectin-associated serine protease. J Immunol 165:2637–2642CrossRefGoogle Scholar
  34. Matsushita M, Kuraya M, Hamasaki N, Tsujimura M, Shiraki H, Fujita T (2002) Activation of the lectin complement pathway by H-ficolin (Hakata antigen). J Immunol 168:3502–3506CrossRefGoogle Scholar
  35. Mizuno Y, Kozutsumi Y, Kawasaki T, Yamashina I (1981) Isolation and characterization of a mannan-binding protein from rat liver. J Biol Chem 256:4247–4252PubMedGoogle Scholar
  36. Rooryck C, Diaz-Font A, Osborn DP, Chabchoub E, Hernandez-Hernandez V, Shamseldin H, Kenny J, Waters A, Jenkins D, Kaissi AA et al (2011) Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome. Nat Genet 43:197–203CrossRefGoogle Scholar
  37. Rosen BS, Cook KS, Yaglom J, Groves DL, Volanakis JE, Damm D, White T, Spiegelman BM (1989) Adipsin and complement factor D activity: an immune-related defect in obesity. Science 244:1483–1487CrossRefGoogle Scholar
  38. Schwaeble WJ, Lynch NJ, Clark JE, Marber M, Samani NJ, Ali YM, Dudler T, Parent B, Lhotta K, Wallis R et al (2011) Targeting of mannan-binding lectin-associated serine protease-2 confers protection from myocardial and gastrointestinal ischemia/reperfusion injury. Proc Natl Acad Sci USA 108:7523–7528CrossRefGoogle Scholar
  39. Selander B, Martensson U, Weintraub A, Holmstrom E, Matsushita M, Thiel S, Jensenius JC, Truedsson L, Sjoholm AG (2006) Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2. J Clin Invest 116:1425–1434CrossRefGoogle Scholar
  40. Sheriff S, Chang CY, Ezekowitz RA (1994) Human mannose-binding protein carbohydrate recognition domain trimerizes through a triple alpha-helical coiled-coil. Nat Struct Biol 1:789–794CrossRefGoogle Scholar
  41. Skjoedt MO, Hummelshoj T, Palarasah Y, Honore C, Koch C, Skjodt K, Garred P (2010) A novel mannose-binding lectin/ficolin-associated protein is highly expressed in heart and skeletal muscle tissues and inhibits complement activation. J Biol Chem 285:8234–8243CrossRefGoogle Scholar
  42. Stover CM, Thiel S, Thelen M, Lynch NJ, Vorup-Jensen T, Jensenius JC, Schwaeble WJ (1999) Two constituents of the initiation complex of the mannan-binding lectin activation pathway of complement are encoded by a single structural gene. J Immunol 162:3481–3490PubMedGoogle Scholar
  43. Sugimoto R, Yae Y, Akaiwa M, Kitajima S, Shibata Y, Sato H, Hirata J, Okochi K, Izuhara K, Hamasaki N (1998) Cloning and characterization of the Hakata antigen, a member of the ficolin/opsonin p35 lectin family. J Biol Chem 273:20721–20727CrossRefGoogle Scholar
  44. Takahashi M, Endo Y, Fujita T, 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 11:859–863CrossRefGoogle Scholar
  45. Takahashi M, Iwaki D, Kanno K, Ishida Y, Xiong J, Matsushita M, Endo Y, Miura S, Ishii N, Sugamura K, Fujita T (2008) Mannose-binding lectin (MBL)-associated serine protease (MASP)-1 contributes to activation of the lectin complement pathway. J Immunol 180:6132–6138CrossRefGoogle Scholar
  46. Takahashi M, Ishida Y, Iwaki D, Kanno K, Suzuki T, Endo Y, Homma Y, Fujita T (2010) Essential role of mannose-binding lectin-associated serine protease-1 in activation of the complement factor D. J Exp Med 207:29–37CrossRefGoogle Scholar
  47. Tanio M, Kondo S, Sugio S, Kohno T (2007) Trivalent recognition unit of innate immunity system: crystal structure of trimeric human M-ficolin fibrinogen-like domain. J Biol Chem 282:3889–3895CrossRefGoogle Scholar
  48. Thiel S, Vorup-Jensen T, Stover CM, Schwaeble W, Laursen SB, Poulsen K, Willis AC, Eggleton P, Hansen S, Holmskov U et al (1997) A second serine protease associated with mannan-binding lectin that activates complement. Nature 386:506–510CrossRefGoogle Scholar
  49. Thielens NM, Cseh S, Thiel S, Vorup-Jensen T, Rossi V, Jensenius JC, Arlaud GJ (2001) Interaction properties of human mannan-binding lectin (MBL)-associated serine proteases-1 and -2, MBL-associated protein 19, and MBL. J Immunol 166:5068–5077CrossRefGoogle Scholar
  50. Vorup-Jensen T, Petersen SV, Hansen AG, Poulsen K, Schwaeble W, Sim RB, Reid KB, Davis SJ, Thiel S, Jensenius JC (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 165:2093–2100CrossRefGoogle Scholar
  51. Walport MJ (2001a) Complement. First of two parts. N Engl J Med 344:1058–1066CrossRefGoogle Scholar
  52. Walport MJ (2001b) Complement. Second of two parts. N Engl J Med 344:1140–1144CrossRefGoogle Scholar
  53. Weis WI, Drickamer K, Hendrickson WA (1992) Structure of a C-type mannose-binding protein complexed with an oligosaccharide. Nature 360:127–134CrossRefGoogle Scholar
  54. White RT, Damm D, Hancock N, Rosen BS, Lowell BB, Usher P, Flier JS, Spiegelman BM (1992) Human adipsin is identical to complement factor D and is expressed at high levels in adipose tissue. J Biol Chem 267:9210–9213PubMedGoogle Scholar
  55. Zundel S, Cseh S, Lacroix M, Dahl MR, Matsushita M, Andrieu JP, Schwaeble WJ, Jensenius JC, Fujita T, Arlaud GJ, Thielens NM (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 172:4342–4350CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Hideharu Sekine
    • 1
  • Minoru Takahashi
    • 1
  • Daisuke Iwaki
    • 1
  • Teizo Fujita
    • 1
    • 2
    Email author
  1. 1.Department of ImmunologyFukushima Medical University School of MedicineFukushimaJapan
  2. 2.Fukushima Prefectural General Hygiene InstituteFukushimaJapan

Personalised recommendations