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Alpha1-microglobulin and bikunin in rats with collagen II-induced arthritis: plasma levels and liver mRNA content
C Falkenberg1, A Blom, E Fries
1Department of Cell and Molecular Biology, Lund University, Sweden.
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 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.
Insights
In collagen-induced arthritis, free bikunin increases and is excreted in urine early on. Later, alpha1-microglobulin-bikunin synthesis rises, with proteins likely directed elsewhere.
Area of Science:
- Biochemistry
- Immunology
- Proteomics
Background:
- Alpha1-microglobulin (alpha1-m) and bikunin, synthesized as a common precursor in the liver, are involved in inflammation.
- The regulation of alpha1-m and bikunin synthesis during inflammatory conditions remains unclear.
Purpose of the Study:
- To investigate the plasma and urinary concentrations and hepatic mRNA levels of alpha1-m and bikunin during collagen-induced arthritis development in rats.
- To correlate these changes with established acute-phase protein responses.
Main Methods:
- Measurement of plasma and urinary alpha1-m and bikunin concentrations.
- Quantification of hepatic alpha1-m-bikunin mRNA levels.
- Assay of plasma acute-phase proteins (fibronectin, alpha1-acid glycoprotein, albumin, alpha1-inhibitor-3).
Main Results:
- A biphasic inflammatory response was observed, with early (1 week) and late (3 weeks) phases characterized by distinct protein profiles.
- Hepatic alpha1-m-bikunin mRNA levels showed a slight decrease at 1 week and an increase at 3 weeks.
- While total plasma alpha1-m and bikunin remained unchanged, free bikunin and the fibronectin/alpha1-m complex elevated at 1 week, with increased urinary bikunin excretion.
Conclusions:
- Early collagen-induced arthritis is associated with increased free bikunin in plasma and enhanced urinary excretion.
- Later in the disease, elevated hepatic synthesis of alpha1-m-bikunin suggests redirection of these proteins.
- These findings provide insights into the dynamic regulation of alpha1-m and bikunin during inflammation.