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Distinct Pathways of Mannan-Binding Lectin (MBL)- and C1-Complex Autoactivation Revealed by Reconstitution of MBL with Recombinant MBL-Associated Serine Protease-2
Abstract
Mannan-binding lectin (MBL) plays a pivotal role in innate immunity by activating complement after binding carbohydrate moieties on pathogenic bacteria and viruses. Structural similarities shared by MBL and C1 complexes and by the MBL- and C1q-associated serine proteases, MBL-associated serine protease (MASP)-1 and MASP-2, and C1r and C1s, respectively, have led to the expectation that the pathways of complement activation by MBL and C1 complexes are likely to be very similar. We have expressed rMASP-2 and show that, whereas C1 complex autoactivation proceeds via a two-step mechanism requiring proteolytic activation of both C1r and C1s, reconstitution with MASP-2 alone is sufficient for complement activation by MBL. The results suggest that the catalytic activities of MASP-2 split between the two proteases of the C1 complex during the course of vertebrate complement evolution.
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Citations
Cited by
Evolution of the lectin–complement pathway and its role in innate immunity
Fujita, T. (2002) · Nature Reviews Immunology · doi:10.1038/nri800 · Cited by 697
The lectin‐complement pathway – its role in innate immunity and evolution
Fujita, T., Matsushita, M., & Endo, Y. (2004) · Immunological Reviews · doi:10.1111/j.0105-2896.2004.0123.x · Cited by 606
Human IgA Activates the Complement System Via the Mannan-Binding Lectin Pathway
Roos, A., Bouwman, L. H., van Gijlswijk-Janssen, D. J., Faber-Krol, M. C., Stahl, G. L., & Daha, M. R. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.5.2861 · Cited by 431
Dahl, M. R., Thiel, S., Matsushita, M., Fujita, T., Willis, A. C., Christensen, T., Vorup-Jensen, T., & Jensenius, J. C. (2001) · Immunity · doi:10.1016/s1074-7613(01)00161-3 · Cited by 397
Self-citationThe complement system: History, pathways, cascade and inhibitors
Nesargikar, P., Spiller, B., & Chavez, R. (2012) · European Journal of Microbiology and Immunology · doi:10.1556/eujmi.2.2012.2.2 · Cited by 324
Metadata
- Authors
- Vorup-Jensen, T., Petersen, S. V., Hansen, A. G., Poulsen, K., Schwaeble, W., Sim, R. B., Reid, K. B. M., Davis, S. J., Thiel, S., & Jensenius, J. C.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-08
- Volume
- 165
- Issue
- 4
- Pages
- 2093-2100
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2164969570
- Cited by
- 202
- References
- 0
- FWCI
- 4.16
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Distinct Pathways of Mannan-Binding Lectin (MBL)- and C1-Complex Autoactivation Revealed by Reconstitution of MBL with Recombinant MBL-Associated Serine Protease-2. https://app.cochat.ai/papers/10.4049/jimmunol.165.4.2093
- The paper
- Vorup-Jensen, T., Petersen, S. V., Hansen, A. G., Poulsen, K., Schwaeble, W., Sim, R. B., Reid, K. B. M., Davis, S. J., Thiel, S., & 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. The Journal of Immunology. https://doi.org/10.4049/jimmunol.165.4.2093
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