Distinct pathways of mannan-binding lectin (MBL)- and C1-complex autoactivation revealed by reconstitution of MBL with recombinant MBL-associated serine protease-2.

T Vorup-Jensen; Steen Vang Petersen; A G Hansen; Knud Poulsen; W Schwaeble; R B Sim; K B Reid; S J Davis; S Thiel; J C Jensenius

Distinct pathways of mannan-binding lectin (MBL)- and C1-complex autoactivation revealed by reconstitution of MBL with recombinant MBL-associated serine protease-2.

T Vorup-Jensen, Steen Vang Petersen, A G Hansen, Knud Poulsen, W Schwaeble, R B Sim, K B Reid, S J Davis, S Thiel, J C Jensenius

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

181 Citations (Scopus)

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.
Udgivelsesdato: 2000-Aug-15

Original language	English
Journal	Journal of Immunology
Volume	165
Issue	4
Pages (from-to)	2093-100
Number of pages	7
ISSN	0022-1767
Publication status	Published - 2000

Keywords

Carrier Proteins
Cell Line
Chromatography, Gel
Cloning, Molecular
Collectins
Complement Activation
Complement C1
Complement C3
Complement C4
Enzyme Activation
Enzyme Precursors
Genetic Vectors
Humans
Lectins
Mannans
Mannose-Binding Protein-Associated Serine Proteases
Recombinant Proteins
Serine Endopeptidases
Signal Transduction

Cite this

@article{83578be0fbd911dcb919000ea68e967b,

title = "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. Udgivelsesdato: 2000-Aug-15",

keywords = "Carrier Proteins, Cell Line, Chromatography, Gel, Cloning, Molecular, Collectins, Complement Activation, Complement C1, Complement C3, Complement C4, Enzyme Activation, Enzyme Precursors, Genetic Vectors, Humans, Lectins, Mannans, Mannose-Binding Protein-Associated Serine Proteases, Recombinant Proteins, Serine Endopeptidases, Signal Transduction",

author = "T Vorup-Jensen and Petersen, {Steen Vang} and Hansen, {A G} and Knud Poulsen and W Schwaeble and Sim, {R B} and Reid, {K B} and Davis, {S J} and S Thiel and Jensenius, {J C}",

year = "2000",

language = "English",

volume = "165",

pages = "2093--100",

journal = "Journal of Immunology",

issn = "0022-1767",

publisher = "American Association of Immunologists",

number = "4",

}

Distinct pathways of mannan-binding lectin (MBL)- and C1-complex autoactivation revealed by reconstitution of MBL with recombinant MBL-associated serine protease-2. / Vorup-Jensen, T; Petersen, Steen Vang; Hansen, A G et al.
In: Journal of Immunology, Vol. 165, No. 4, 2000, p. 2093-100.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Distinct pathways of mannan-binding lectin (MBL)- and C1-complex autoactivation revealed by reconstitution of MBL with recombinant MBL-associated serine protease-2.

AU - Vorup-Jensen, T

AU - Petersen, Steen Vang

AU - Hansen, A G

AU - Poulsen, Knud

AU - Schwaeble, W

AU - Sim, R B

AU - Reid, K B

AU - Davis, S J

AU - Thiel, S

AU - Jensenius, J C

PY - 2000

Y1 - 2000

N2 - 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. Udgivelsesdato: 2000-Aug-15

AB - 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. Udgivelsesdato: 2000-Aug-15

KW - Carrier Proteins

KW - Cell Line

KW - Chromatography, Gel

KW - Cloning, Molecular

KW - Collectins

KW - Complement Activation

KW - Complement C1

KW - Complement C3

KW - Complement C4

KW - Enzyme Activation

KW - Enzyme Precursors

KW - Genetic Vectors

KW - Humans

KW - Lectins

KW - Mannans

KW - Mannose-Binding Protein-Associated Serine Proteases

KW - Recombinant Proteins

KW - Serine Endopeptidases

KW - Signal Transduction

M3 - Journal article

C2 - 10925294

SN - 0022-1767

VL - 165

SP - 2093

EP - 2100

JO - Journal of Immunology

JF - Journal of Immunology

IS - 4

ER -