Glycoprotein biosynthesis during the acute-phase response to inflammation

Abstract

Inflammation results in an increase in the levels of a variety of glycoproteins in serum. The glycoproteins that respond in this way are usually referred to as acute-phase reactants. Studies on the acute-phase response of rat alpha 1-acid glycoprotein showed that there was an increase in the liver levels of this glycoprotein at 12 h after turpentine inflammation. This was followed by increased serum levels at 48-72 h after inflammation, suggesting a precursor-product relationship between liver and serum alpha 1-acid glycoprotein. Incorporation studies coupled with measurements of synthesis rates of alpha 1-acid glycoprotein showed that increased synthesis was responsible for the acute-phase response of this protein to inflammation. These studies also showed that albumin was a negative acute-phase reactant. The acute-phase response of alpha 1-acid glycoprotein was accompanied by increased liver pools of UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-N-acetylgalactosamine (UDP-GalNAc) and increased liver activities of glucosamine-6-phosphate synthase and UDP-GlcNAc 2-epimerase. Activities of galactosyl and sialyl transferases in liver were also elevated and serum sialyl transferase was increased substantially in inflammation, suggesting that it may also be an acute-phase reactant. Liver activities of beta-N-acetylhexosaminidase and beta-galactosidase declined by about 50% at 24 h after inflammation; there was evidence that serum levels of these enzymes increased at 24-72 h after inflammation, suggesting that the lysosomal glycosidases may be released from liver during inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

Bioinformatics analysis of the early inflammatory response in a rat thermal injury model

“…Cluster 2 is enriched in genes involved in this particular pathway. It was also recently observed [28] that the acute-phase response is accompanied by increased liver pools of N-acetylglucosamine at about 12 h post inflammation. Consistent with this observation, Cluster 1 is enriched in genes of that ontology.…”

Interpretation of Plasma Protein Measurements in End-Stage Renal Disease

“…The acute-phase response is initiated by cytokines that are released either in the circulation by mononuclear cells (Th-1 cells and macrophages) or locally by Kupffer cells and signal a cascade of events within hepatocytes [39,40]. Synthesis of positive acutephase reactant proteins, including fibrinogen, C-reactive protein (CRP), · 1 -acid glycoprotein [41], · 2 -macroglobulin and serum amyloid A (SAA) is stimulated [42][43][44][45], and synthesis of negative acute-phase reactive proteinsusually presumed to be nutritional markers (albumin [25], prealbumin [46][47][48][49], transferrin [44,50] reactive proteins is increased in plasma, while that of albumin is reduced. Thus, if hypoalbuminemia in ESRD patients is a consequence of a reduced rate of albumin synthesis, reduced albumin synthesis could be a consequence of protein malnutrition or the acute-phase response or a combination of these processes.…”

Albumin Turnover in Renal Disease

“…The acute-phase response is initiated by cytokines that are released either systematically or locally by Kupffer cells and signal a cascade of events within hepatocytes [18,19]. Synthesis of positive acute-phase reactant proteins, including fibrinogen, C-reactive protein (CRP), · 2 -macroglobulin, and serum amyloid A (SAA) is also stimulated [20][21][22][23]. In contrast, the synthesis of negative acutephase reactive proteins, usually presumed to be markers of nutritional status (e.g., albumin [19], prealbumin and apoA-I [24]) are suppressed.…”