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Cooperation between MASP-1 and MASP-2 in the generation of C3 convertase through the MBL pathway

Moller-Kristensen, Mette; Thiel, Steffen; Sjöholm, Anders LU ; Matsushita, Misao and Jensenius, Jens C. (2007) In International Immunology 19(2). p.141-149
Abstract
The complement system is an important part of the innate immune system. Three pathways, the classical, the alternative and the lectin pathway, lead to the cleavage of complement factor C3, a central event in the activation of the complement system. We investigated the deposition of C3b (solid-phase C3 activation product) on a mannan-coated surface at high concentration of human serum (17%). At these conditions, mannan-binding lectin (MBL) promoted the activation of C3 through the combined action of MBL-associated serine protease (MASP)-1 and MASP-2 without appreciable involvement of the alternative pathway. In serum depleted of MASP-1, MASP-2 and MASP-3, we observed synergetic effect of reconstitution with MASP-1 and MASP-2. This was... (More)
The complement system is an important part of the innate immune system. Three pathways, the classical, the alternative and the lectin pathway, lead to the cleavage of complement factor C3, a central event in the activation of the complement system. We investigated the deposition of C3b (solid-phase C3 activation product) on a mannan-coated surface at high concentration of human serum (17%). At these conditions, mannan-binding lectin (MBL) promoted the activation of C3 through the combined action of MBL-associated serine protease (MASP)-1 and MASP-2 without appreciable involvement of the alternative pathway. In serum depleted of MASP-1, MASP-2 and MASP-3, we observed synergetic effect of reconstitution with MASP-1 and MASP-2. This was inhibited by MASP-3. No C3b deposition was observed with C2- or C4-depleted serum. Depletion of factor B had no effect on the MBL-MASP-promoted C3b deposition. Our results demonstrate a function of the orphan protease MASP-1 by providing evidence that this enzyme collaborates with MASP-2 in the generation of C3 convertase, a process observable at high serum concentration, but not at low serum concentration. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
complement, lectin pathway, C3 activation, mannan-binding lectin
in
International Immunology
volume
19
issue
2
pages
141 - 149
publisher
Oxford University Press
external identifiers
  • wos:000243805900004
  • scopus:33846618236
ISSN
1460-2377
DOI
10.1093/intimm/dxl131
language
English
LU publication?
yes
id
8f827532-4e8c-4bc5-818f-c24556f1195e (old id 676276)
date added to LUP
2007-12-18 11:56:58
date last changed
2017-06-04 03:31:06
@article{8f827532-4e8c-4bc5-818f-c24556f1195e,
  abstract     = {The complement system is an important part of the innate immune system. Three pathways, the classical, the alternative and the lectin pathway, lead to the cleavage of complement factor C3, a central event in the activation of the complement system. We investigated the deposition of C3b (solid-phase C3 activation product) on a mannan-coated surface at high concentration of human serum (17%). At these conditions, mannan-binding lectin (MBL) promoted the activation of C3 through the combined action of MBL-associated serine protease (MASP)-1 and MASP-2 without appreciable involvement of the alternative pathway. In serum depleted of MASP-1, MASP-2 and MASP-3, we observed synergetic effect of reconstitution with MASP-1 and MASP-2. This was inhibited by MASP-3. No C3b deposition was observed with C2- or C4-depleted serum. Depletion of factor B had no effect on the MBL-MASP-promoted C3b deposition. Our results demonstrate a function of the orphan protease MASP-1 by providing evidence that this enzyme collaborates with MASP-2 in the generation of C3 convertase, a process observable at high serum concentration, but not at low serum concentration.},
  author       = {Moller-Kristensen, Mette and Thiel, Steffen and Sjöholm, Anders and Matsushita, Misao and Jensenius, Jens C.},
  issn         = {1460-2377},
  keyword      = {complement,lectin pathway,C3 activation,mannan-binding lectin},
  language     = {eng},
  number       = {2},
  pages        = {141--149},
  publisher    = {Oxford University Press},
  series       = {International Immunology},
  title        = {Cooperation between MASP-1 and MASP-2 in the generation of C3 convertase through the MBL pathway},
  url          = {http://dx.doi.org/10.1093/intimm/dxl131},
  volume       = {19},
  year         = {2007},
}