Advanced

Binding and inhibition of myeloperoxidase (MPO): a major function of ceruloplasmin?

Segelmark, Mårten LU ; Persson, B; Hellmark, Thomas LU and Wieslander, Jörgen LU (1997) In Clinical and Experimental Immunology 108(1). p.167-174
Abstract
Interactions between plasma proteins and MPO were studied. The protein fraction of normal plasma and serum was shown to exhibit an inhibitory effect on the peroxidase activity of MPO. Most of the inhibitory effect could be retained on an MPO-coupled affinity chromatography column. In particular, a protein with apparent mol. wt of 130 kD showed affinity for MPO. The protein was identified as ceruloplasmin by N-terminal amino acid sequencing and immunochemistry. During separation procedures the peroxidase inhibitory effect was limited to ceruloplasmin-containing fractions of plasma. Purified ceruloplasmin inhibited the peroxidase activity of MPO in a concentration-dependent manner, and exhibited selective binding to MPO-coated microtitre... (More)
Interactions between plasma proteins and MPO were studied. The protein fraction of normal plasma and serum was shown to exhibit an inhibitory effect on the peroxidase activity of MPO. Most of the inhibitory effect could be retained on an MPO-coupled affinity chromatography column. In particular, a protein with apparent mol. wt of 130 kD showed affinity for MPO. The protein was identified as ceruloplasmin by N-terminal amino acid sequencing and immunochemistry. During separation procedures the peroxidase inhibitory effect was limited to ceruloplasmin-containing fractions of plasma. Purified ceruloplasmin inhibited the peroxidase activity of MPO in a concentration-dependent manner, and exhibited selective binding to MPO-coated microtitre plates. This binding could be inhibited by MPO dissolved in buffer. Correspondingly the binding of MPO to ceruloplasmin-coated plates could be blocked by ceruloplasmin in solution, showing a physical interaction to occur between the two proteins under physiological conditions. We also found affinity to exist between MPO and C3 (and its C3d-containing fragments). However, C3 and C3 fragments did not inhibit the peroxidase reaction in vitro. We propose that ceruloplasmin takes part in the clearance and inactivation of MPO, in vivo. We also speculate that impaired inactivation of MPO may have a pathophysiological role in inflammatory diseases characterized by autoantibodies to MPO, such as rapidly progressive glomerulonephritis with P-ANCA (perinuclear anti-neutrophil cytoplasmic antibodies). (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
myeloperoxidase, ceruloplasmin, complement C3d, glomerulonephritis, ANCA
in
Clinical and Experimental Immunology
volume
108
issue
1
pages
167 - 174
publisher
British Society for Immunology
external identifiers
  • pmid:9097926
  • scopus:0030894460
ISSN
0009-9104
DOI
10.1046/j.1365-2249.1997.d01-992.x
language
English
LU publication?
yes
id
9a48ea5b-f70f-4e8c-b1d1-32586c17ee52 (old id 1111851)
date added to LUP
2008-07-18 14:17:56
date last changed
2017-09-17 05:22:16
@article{9a48ea5b-f70f-4e8c-b1d1-32586c17ee52,
  abstract     = {Interactions between plasma proteins and MPO were studied. The protein fraction of normal plasma and serum was shown to exhibit an inhibitory effect on the peroxidase activity of MPO. Most of the inhibitory effect could be retained on an MPO-coupled affinity chromatography column. In particular, a protein with apparent mol. wt of 130 kD showed affinity for MPO. The protein was identified as ceruloplasmin by N-terminal amino acid sequencing and immunochemistry. During separation procedures the peroxidase inhibitory effect was limited to ceruloplasmin-containing fractions of plasma. Purified ceruloplasmin inhibited the peroxidase activity of MPO in a concentration-dependent manner, and exhibited selective binding to MPO-coated microtitre plates. This binding could be inhibited by MPO dissolved in buffer. Correspondingly the binding of MPO to ceruloplasmin-coated plates could be blocked by ceruloplasmin in solution, showing a physical interaction to occur between the two proteins under physiological conditions. We also found affinity to exist between MPO and C3 (and its C3d-containing fragments). However, C3 and C3 fragments did not inhibit the peroxidase reaction in vitro. We propose that ceruloplasmin takes part in the clearance and inactivation of MPO, in vivo. We also speculate that impaired inactivation of MPO may have a pathophysiological role in inflammatory diseases characterized by autoantibodies to MPO, such as rapidly progressive glomerulonephritis with P-ANCA (perinuclear anti-neutrophil cytoplasmic antibodies).},
  author       = {Segelmark, Mårten and Persson, B and Hellmark, Thomas and Wieslander, Jörgen},
  issn         = {0009-9104},
  keyword      = {myeloperoxidase,ceruloplasmin,complement C3d,glomerulonephritis,ANCA},
  language     = {eng},
  number       = {1},
  pages        = {167--174},
  publisher    = {British Society for Immunology},
  series       = {Clinical and Experimental Immunology},
  title        = {Binding and inhibition of myeloperoxidase (MPO): a major function of ceruloplasmin?},
  url          = {http://dx.doi.org/10.1046/j.1365-2249.1997.d01-992.x},
  volume       = {108},
  year         = {1997},
}