Glycoprotein biosynthesis during the acute-phase response to inflammation

Area of Science:

• Biochemistry
• Immunology
• Molecular Biology

Background:

• Inflammation triggers changes in serum glycoprotein levels, termed acute-phase reactants.
• Alpha 1-acid glycoprotein (AAG) is a known acute-phase reactant.
• Albumin serves as a negative acute-phase reactant.

Purpose of the Study:

• To investigate the mechanism behind the acute-phase response of rat alpha 1-acid glycoprotein.
• To explore the role of glycosylation pathways and related enzymes in inflammation.
• To examine the changes in lysosomal glycosidases during the acute-phase response.

Main Methods:

• Turpentine-induced inflammation model in rats.
• Measurement of glycoprotein levels in liver and serum.
• Incorporation studies and synthesis rate measurements.
• Assays for liver and serum enzyme activities (glycosyltransferases, lysosomal glycosidases).

Main Results:

• Increased liver AAG levels preceded increased serum AAG levels, suggesting a precursor-product relationship.
• Enhanced synthesis of AAG was identified as the primary driver of its acute-phase response.
• Elevated liver pools of UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine, along with increased activities of related enzymes, were observed.
• Increased activities of liver galactosyl and sialyl transferases, and elevated serum sialyl transferase were noted.
• Decreased liver activities and increased serum levels of lysosomal glycosidases (beta-N-acetylhexosaminidase, beta-galactosidase) suggest release from the liver.

Conclusions:

• The acute-phase response of alpha 1-acid glycoprotein is primarily mediated by increased hepatic synthesis.
• Inflammation alters the metabolic pathways of glycosylation, impacting AAG production.
• Lysosomal glycosidases may be released from the liver into circulation during inflammation.