Alpha1-microglobulin and bikunin in rats with collagen II-induced arthritis: plasma levels and liver mRNA content.
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.
Falkenberg
C
C
Department of Cell and Molecular Biology, Lund University, Sweden.
Blom
A
A
Fries
E
E
Ekström
G
G
Särnstrand
B
B
Salier
J P
JP
Akerström
B
B
D000209:Acute-Phase Proteins / Q000378:metabolism; D000510:Alpha-Globulins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000378:metabolism*; D003094:Collagen; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D008099:Liver / Q000378:metabolism*; D008562:Membrane Glycoproteins; D009961:Orosomucoid / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D015842:Serine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism*; D014360:Trypsin Inhibitor, Kunitz Soybean
D000209:Acute-Phase Proteins; D000510:Alpha-Globulins; D005353:Fibronectins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D009961:Orosomucoid; D012333:RNA, Messenger; C109148:SPINT2 protein, human; D015842:Serine Proteinase Inhibitors; C017894:alpha 1-inhibitor 3; C016001:alpha-1-microglobulin; D003094:Collagen; D014360:Trypsin Inhibitor, Kunitz Soybean