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Alpha1-microglobulin and bikunin in rats with collagen II-induced arthritis : plasma levels and liver mRNA content

Falkenberg, C LU ; Blom, A ; Fries, E ; Ekström, G ; Särnstrand, B LU ; Salier, J P and Åkerström, B LU (1997) In Scandinavian Journal of Immunology 46(2). p.8-122
Abstract

The plasma proteins alpha1-microglobulin (alpha1-m) and bikunin are synthesized in the liver as a common precursor which is cleaved just before secretion. Half of plasma alpha1-m is covalently linked to fibronectin and alpha1-inhibitor-3, and more than 95% of bikunin is part of pre-alpha-inhibitor, inter-alpha-inhibitor and related large molecules. Both alpha1-m and bikunin have been shown to be involved in inflammation, but the regulation of their synthesis is not clear. The authors have measured the plasma and urinary concentrations of alpha1-m and bikunin as well as their hepatic mRNA levels in rats during the development of collagen-induced arthritis. Also, the plasma concentrations of acknowledged acute-phase proteins were... (More)

The plasma proteins alpha1-microglobulin (alpha1-m) and bikunin are synthesized in the liver as a common precursor which is cleaved just before secretion. Half of plasma alpha1-m is covalently linked to fibronectin and alpha1-inhibitor-3, and more than 95% of bikunin is part of pre-alpha-inhibitor, inter-alpha-inhibitor and related large molecules. Both alpha1-m and bikunin have been shown to be involved in inflammation, but the regulation of their synthesis is not clear. The authors have measured the plasma and urinary concentrations of alpha1-m and bikunin as well as their hepatic mRNA levels in rats during the development of collagen-induced arthritis. Also, the plasma concentrations of acknowledged acute-phase proteins were measured. The results suggested a biphasic inflammatory reaction: an early response after 1 week, represented by an elevated fibronectin level; and a late response after 3 weeks, represented by elevated alpha1-acid glycoprotein and decreased albumin and alpha1-inhibitor-3 levels. The alpha1-m-bikunin mRNA content in liver was slightly reduced after 1 week and elevated after 3 weeks, but the total concentrations of free and bound alpha1-m and bikunin in plasma were unchanged. The free bikunin fraction as well as the fibronectin/alpha1-m complex in plasma, however, were elevated after 1 week. Urinary bikunin levels were also elevated after 1 week, whereas urinary alpha1-m levels remained unchanged. The results thus suggest that free bikunin in plasma is increased and excreted in the urine at an early stage during the development of collagen-induced arthritis. Later, when the synthesis rate of alpha1-m-bikunin is elevated, both proteins are most likely directed to other locations in the body.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Acute-Phase Proteins/metabolism, Alpha-Globulins/genetics, Animals, Arthritis, Experimental/chemically induced, Collagen, Female, Fibronectins/metabolism, Glycoproteins/genetics, In Situ Hybridization, Liver/metabolism, Membrane Glycoproteins, Orosomucoid/metabolism, RNA, Messenger/metabolism, Radioimmunoassay, Rats, Serine Proteinase Inhibitors/genetics, Trypsin Inhibitor, Kunitz Soybean
in
Scandinavian Journal of Immunology
volume
46
issue
2
pages
8 - 122
publisher
Wiley-Blackwell
external identifiers
  • pmid:9583992
  • scopus:0030609206
ISSN
0300-9475
DOI
10.1046/j.1365-3083.1997.d01-103.x
language
English
LU publication?
yes
id
a1d7bef9-955e-4b55-bcb5-114b69e449b7
date added to LUP
2019-05-22 10:16:59
date last changed
2024-01-01 06:41:12
@article{a1d7bef9-955e-4b55-bcb5-114b69e449b7,
  abstract     = {{<p>The plasma proteins alpha1-microglobulin (alpha1-m) and bikunin are synthesized in the liver as a common precursor which is cleaved just before secretion. Half of plasma alpha1-m is covalently linked to fibronectin and alpha1-inhibitor-3, and more than 95% of bikunin is part of pre-alpha-inhibitor, inter-alpha-inhibitor and related large molecules. Both alpha1-m and bikunin have been shown to be involved in inflammation, but the regulation of their synthesis is not clear. The authors have measured the plasma and urinary concentrations of alpha1-m and bikunin as well as their hepatic mRNA levels in rats during the development of collagen-induced arthritis. Also, the plasma concentrations of acknowledged acute-phase proteins were measured. The results suggested a biphasic inflammatory reaction: an early response after 1 week, represented by an elevated fibronectin level; and a late response after 3 weeks, represented by elevated alpha1-acid glycoprotein and decreased albumin and alpha1-inhibitor-3 levels. The alpha1-m-bikunin mRNA content in liver was slightly reduced after 1 week and elevated after 3 weeks, but the total concentrations of free and bound alpha1-m and bikunin in plasma were unchanged. The free bikunin fraction as well as the fibronectin/alpha1-m complex in plasma, however, were elevated after 1 week. Urinary bikunin levels were also elevated after 1 week, whereas urinary alpha1-m levels remained unchanged. The results thus suggest that free bikunin in plasma is increased and excreted in the urine at an early stage during the development of collagen-induced arthritis. Later, when the synthesis rate of alpha1-m-bikunin is elevated, both proteins are most likely directed to other locations in the body.</p>}},
  author       = {{Falkenberg, C and Blom, A and Fries, E and Ekström, G and Särnstrand, B and Salier, J P and Åkerström, B}},
  issn         = {{0300-9475}},
  keywords     = {{Acute-Phase Proteins/metabolism; Alpha-Globulins/genetics; Animals; Arthritis, Experimental/chemically induced; Collagen; Female; Fibronectins/metabolism; Glycoproteins/genetics; In Situ Hybridization; Liver/metabolism; Membrane Glycoproteins; Orosomucoid/metabolism; RNA, Messenger/metabolism; Radioimmunoassay; Rats; Serine Proteinase Inhibitors/genetics; Trypsin Inhibitor, Kunitz Soybean}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{8--122}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Scandinavian Journal of Immunology}},
  title        = {{Alpha1-microglobulin and bikunin in rats with collagen II-induced arthritis : plasma levels and liver mRNA content}},
  url          = {{http://dx.doi.org/10.1046/j.1365-3083.1997.d01-103.x}},
  doi          = {{10.1046/j.1365-3083.1997.d01-103.x}},
  volume       = {{46}},
  year         = {{1997}},
}